Immunotropic drugs. Immunomodulators of microbial origin Preparations of microbial origin

The group of immunomodulators includes drugs of animal, microbial, yeast and synthetic origin, which have the specific ability to stimulate immune processes and activate immunocompetent cells (T- and B-lymphocytes) and additional immune factors (macrophages). Strengthening the overall resistance of the body can, to one degree or another, occur under the influence of a number of stimulants and tonics (caffeine, eleutherococcus), vitamins, dibazole, pyrimidine derivatives - methyluracil, pentoxyl (accelerate regeneration, intensify leukopoiesis), derivatives of nucleic acids and biogenic drugs that have received common name - adaptogens. The ability of these drugs to increase the body's resistance and accelerate regeneration processes served as the basis for widespread use in complex therapy of sluggish regenerative processes, infectious, infectious-inflammatory and other diseases. In recent years, the study of the immunological properties of endogenous compounds - lymphokines, interferons has become especially important (the therapeutic effectiveness of a number of drugs - prodigiosan, poludanum, arbidol - is explained to a certain extent by the fact that they stimulate the formation of endogenous interferon, i.e. they are interferonogens).

Preparations prepared on the basis of cytokines are mainly used to correct immunodeficiency states that develop in infectious and oncological diseases, and to prevent complications during radiotherapy and chemotherapy of cancer patients.
One of the promising areas is the use of cytokine preparations as immunoadjuvants for vaccination. The adjuvant effect is enhanced if combinations of cytokines are used.
Some biological substances may contain an admixture of cytokines if activated cells are used for their production. For example, viral vaccines, which are produced using human or monkey cells, contain a wide range of cytokines, including anti-inflammatory cytokines (IL-1, IL-6, TNF). Natural IF preparations obtained from human leukocytes or fibroblasts also contain admixtures of other cytokines that can enhance the immunomodulatory effect of IF preparations.
Recombinant cytokines differ in their activity from mediators of natural origin. A wider range of immunomodulatory effects of natural IF depends on the high degree of glycosylation that occurs during the natural synthesis of the cytokine, and on the presence in the preparations of accompanying cytokines that are formed from cells during cultivation with interferonogen. The therapeutic effect observed when using IF to treat infections, including viral ones, largely depends on the properties of accompanying cytokines.
More than 20 dosage forms of IF are used on the domestic market, intended for various routes of administration.
Human leukocyte dry interferon is synthesized by leukocytes of donor blood in response to the influence of the inducer virus. Has a wide spectrum of antiviral action. Used for the prevention and treatment of influenza and other acute respiratory viral infections. Contraindications and side effects have not been established. Should be used with caution in persons with hypersensitivity to antibiotics and chicken proteins. Apply by spraying or dropping an aqueous solution into the nose. Available in ampoules.
Leukinferon dry injection is a complex preparation consisting of IF-α mixed with other cytokines (IL-1, IL-6, TNF). Enhances the expression of MHC antigens and all hematopoietic germs. It is used to correct secondary and immunodeficiency conditions in acute and chronic infections of various etiologies, to restore hematopoiesis and functional activity of effector cells in cancer patients during cytostatic treatment, for the treatment of influenza and other viral infections. Combination with other immunocorrective drugs is possible. There are no contraindications. It is possible to increase body temperature by 1-1.5ºC. The main method of administration is intramuscular. The daily dose for children under 1 year is 5000 IU, for children over 1 year, adolescents and adults – 10,000 IU. Available in ampoules of 10,000 IU.
Human leukocyte interferon for injection consists of individual components of IF-α. It has immunomodulatory, antiviral and antiproliferative effects. It is used to treat viral infections, multiple sclerosis, hematological malignancies, juvenile respiratory papillomatosis, and solid tumors. No contraindications have been established. During pregnancy, the drug is administered only for health reasons. In case of severe heart disease, the drug is used with caution. When a dose exceeding 500,000 IU is administered, a flu-like syndrome may occur. Doses and regimens of use depend on the nosological form of the disease. Available in ampoules of 100,000-3,000,000 IU.
Reaferon is a recombinant α-interferon synthesized in the culture of Pseudomonas spp. or E. coli. It has immunomodulatory, antiviral and antitumor effects. Used to treat viral infections, cancer, essential thrombocytopenia, multiple sclerosis. Contraindicated in severe forms of allergic diseases and pregnancy. With parenteral administration, a flu-like syndrome, leukemia and thrombocytopenia may occur, with local administration - an inflammatory reaction, with instillation - conjunctivitis. Doses and regimens of drug administration depend on the nosological form of the disease. Available in ampoules and vials from 500,000 to 5,000,000 IU.
Realdiron for injection dry is a human recombinant IF-α synthesized by the culture of Pseudomonas putida. Indications, contraindications, side effects are the same as for reaferon. Preparations for oral use (Lipint), in the form of eye drops (Lokferon), nasal drops (Grippferon), ointments (Intergen, Viferon-ointment), suppositories (Sveferon, Viferon-suppositories), in combination with gel (Infagel) are also produced. and normal immunoglobulin (Kipferon).
Colony-stimulating factors
3 types of colony-stimulating factors were obtained: G-CSF, M-CSF and GM-CSF. They affect bone marrow hematopoiesis, restoring the quantitative and qualitative indicators of granulocytes and macrophages. Some cytokines (betaleukin, roncoleukin) are administered intravenously. With intravenous and even local administration of cytokines, individual adverse reactions (fever, headache, local reactions) and even syndromes may occur.

Syndromes that occur after cytokine administration
Syndrome	Cytokines
Flu-like syndrome	IL-1, IL-2, IL-3, G-CSF, GM-CSF
A syndrome similar to septic shock	TNF, IL-1, IL-2, IL-6
Cachexia	TNF, IL-6
Capillary leak syndrome	IL-2, GM-CSF, TNF

The normal microflora of open body cavities is one of the factors of natural resistance that ensures a natural state of homeostasis. The composition of the intestinal microflora in humans is relatively constant, but depends on nutrition, lifestyle, climatic conditions and other factors. The microflora changes unfavorably with long-term use of antibiotics and chemotherapy, stress and immunodeficiency states, disruption of the ecology and physicochemical barriers of the intestinal mucosa.
Normal intestinal microflora competitively displaces pathogenic microflora and has a strong nonspecific effect on the immune system, primarily on the intestinal lymphoid tissue. Probiotics have a strong polyclonal property; under the influence of microflora, the complement system and phagocytes are activated, the production of IgM, normal secretory antibodies to antigens common with antigens of pathogenic flora is enhanced. IgA1 is able to attach to the surface of the mucous membrane due to heavy chains, and IgA2 enters the intestinal lumen and ensures the inactivation of pathogens.
The use of eubiotics as therapeutic and prophylactic agents is designed to stimulate all forms of resistance: competition with pathogens, colonization, immunostimulating effects, synthesis of antibiotic substances, formation of lactic and acetic acids that prevent the proliferation of pathogenic, putrefactive and gas-forming microflora, inactivation of alkaline phosphatase and enterokinase, vitamin formation and absorption of vitamins from the intestines.
The immune response is stimulated by:
1. increasing the phagocytic activity of leukocytes;
2. increasing the concentration of lysozyme in the intestines;
3. activation of NK cells;
4. normalization of the content of CD3-, CD4-, CD8 cells and the CD4/CD8 ratio;
5. increased production of cytokines: IL-1, 2, 5, 6, 10, TNFα, IF;
6. increasing the level of IgM, normal antibodies and secretory IgA in the intestine.
The main mechanisms of the protective effect of eubiotics appear regardless of the method of drug administration (oral, vaginal, rectal). Many representatives of normal flora exhibit synergistic action, which is important for the development of complex drugs.
Eubiotic preparations are prepared from living representatives of the normal microflora of the human intestine: Escherichia coli (colibacterin, bificol), bifidobacteria (bifidumbacterin, bifidumbacterin forte, bifilis), lactobacilli (lactobacterin, acylact, acipol). In recent years, for the treatment of dysbiosis, domestic drugs made from living non-pathogenic antagonistically active representatives of the genus Bacillus have been introduced into medical practice: sporobacteria, bactisporin, biosporin.
When taken orally, the living microorganisms contained in the drug quickly populate the intestines, thereby helping to normalize the biocenosis and restore the digestive, metabolic and protective functions of the gastrointestinal tract. The mechanism of action of these drugs is similar for other methods of administration, for example vaginal.
All eubiotic drugs are characterized by extremely rare adverse reactions and, as a result, there are no contraindications to their use. Eubiotics can be used simultaneously with chemotherapy and antibiotic therapy. Most eubiotics (bifidumbacterin, lactobacterin, acipol, acylact, bifiliz) are used from the first day of a child’s life.
Eubiotics are also used as biologically active additives (BAA) to food.

The babies are not well developed. Therefore, it is not always able to resist various viral attacks. Doctors recommend that parents of such babies maintain and strengthen their immune system. Much attention is paid to hardening and playing sports. In addition, the child must eat food containing all the vitamins and microelements necessary for his growth and development. For some children, such measures are not enough. In such cases, the doctor may prescribe immunostimulating drugs.

What are they needed for?

If the baby is sick for a long time and often, any diseases are quite difficult, there is reason to think about means that will contribute to the body’s resistance to various infections; general measures are used. Sometimes doctors recommend taking immunostimulating drugs.

General measures include:

hardening (it can be started from 3-4 years);
multivitamin preparations (such complexes are recommended by the pediatrician).

Immunostimulating drugs should only be prescribed by a doctor. He will thoroughly examine the baby. Carefully examine all records of the child’s illnesses. And only if the baby’s immunodeficiency is confirmed, will he be prescribed appropriate medications. In another situation, the doctor will advise resorting to general measures.

Immunostimulating agents for children help increase the activity of the body's own defenses. They improve resistance to diseases and infections.

Classification of drugs

There are the following types of immunostimulating drugs that are used for children:

interferons (“Grippferon”, “Viferon”);
interferon inducers (“Amiksin”, “Arbidol”, “Cycloferon”);
drugs from the thymus gland (“Thymostimulin”, “Vilozen”);
herbal medicines (“Echinacea”, “Immunal”);
bacterial agents (“Ribomunil”, “IRS-19”, “Imudon”).

Parents should remember that such drugs must be used very carefully. Incorrect or prolonged use can seriously undermine the defenses of the child's body.

When should you take medications?

It is reliably known that in all inflammatory reactions, immunity plays a decisive role in the course of the pathology. A strong body quickly copes with any disease.

It is almost impossible to protect a child from viruses. Therefore, the most common childhood disease is ARVI. However, some babies get sick for a very long time. Others suffer from colds almost unnoticeably and painlessly. It is in such cases that it is determined whether the child’s immunity is weak or strong. However, do not forget that only a doctor can confirm the child’s pain.

Doctors prescribe immunostimulating agents in the following cases:

The child often experiences recurrent viral, bacterial or fungal infections. They do not respond well to conventional treatment methods.
The baby suffered from colds more than 6 times a year.
Infectious pathologies are very difficult. A number of complications are often observed.
Any illness drags on for a long time. The body reacts very poorly to treatment.
Commonly accepted measures do not provide a positive result.
During diagnosis, immune deficiency was revealed.

It is very important to understand that immunostimulating medications are not a panacea for any ailment. These are medications that have contraindications and can cause unwanted reactions.

Effective drugs

If your baby experiences at least a few of the symptoms described above, you should consult a doctor. After examining the baby and confirming the presence of immunodeficiency, the doctor will prescribe the appropriate medications. They will increase the protective properties of the child’s body.

Doctors provide a whole list of immunostimulating drugs that can be prescribed to children:

"Immunal";
"Echinacea";
Chinese;
"Imudon";
"Ribomunil";
"Lykopid";
"Derinat";
"Amiksin";
"Irs-19";
"Arbidol";
interferons: “Viferon”, “Grippferon”, “Cycloferon”;
"Vilosen";
"Thymostimulin";
"Isoprinosine";
"Broncho-munal";
"Pentoxyl".

Special Cautions

Any of these medications are great for strengthening the immune system. However, it must be used with extreme caution. If these drugs are used for a long time, they can cause harm. After all, under their influence the body is seriously weakened.

It is important to understand that immunostimulating drugs will only be beneficial if the dosage and regimen of the medication have been correctly prescribed to the small patient. Let's look at the most popular ones.

The drug "Arpeflu"

This is a drug that belongs to the group of immunostimulants and is intended for the prevention and treatment of diseases caused by the influenza virus. The drug "Arpeflu", the price of which is quite low, has an excellent antiviral effect. In addition, it stimulates protective reactions and promotes the production of interferon. As a result of such exposure, the body can fight even those viruses that have already penetrated the cells of the mucous membranes. It helps to shorten the duration of the disease and reduces the duration of the pathology.

Indications for the use of the drug "Arpeflu" are:

colds caused by influenza viruses;
prevention of ARVI;
immunodeficiency states;
chronic bronchitis (in complex therapy);
herpetic infection;
prevention of complications after surgery.

You should not use this remedy in case of individual hypersensitivity to it. The medicine is contraindicated for children under 3 years of age. Pregnant and lactating women can use the drug, but require an individual approach and prescription.

Side effects are very rare. These may be allergic reactions:

hives;
swelling.

In most cases, Arpeflu is well tolerated by patients.

The price of this product is about 56 rubles.

Echinacea tincture

The herbal preparation is considered a good immunostimulant. It perfectly strengthens the defenses, suppresses the activity of herpes and influenza viruses. Able to protect against many pathogenic bacteria.

Echinacea is indicated (the price of the tincture is quite reasonable) for the treatment and prevention of viral, colds, and bacterial pathologies of various etiologies. It is appropriate to prescribe such a drug in the case of Sometimes it is recommended for children after regular physical activity in order to strengthen the body.

Contraindications to taking this setting are:

pregnancy;
age up to 7 years;
lactation period;
autoimmune pathologies;
liver and kidney diseases;
allergic reactions.

The drug is easily tolerated by almost any organism. Side effects were observed only in isolated cases. Among the manifestations were:

chills;
symptoms of dyspepsia;
allergic reactions on the skin.

Taking the tincture does not require giving up driving. Since Echinacea has no effect on concentration.

The price of the tincture is approximately 157 rubles.

Medicine "Viferon"

This is an excellent immunostimulating drug with an antiviral effect. The medicine is available in 3 forms:

candles;
ointment;
gel.

The drug "Viferon" is used for children in the form of rectal suppositories. Thanks to this, the medicine does not have a negative effect and causes very few side effects.

This remedy is prescribed for the following infections in complex therapy:

ARVI;
flu;
bacterial uncomplicated pathologies;
herpes;
sepsis;
meningitis;
chronic viral hepatitis.

The medicine "Viferon" can be used for children from birth. This drug is suitable even for premature babies.

The only contraindication to the use of the drug is individual sensitivity to this drug.

Side effects may sometimes include itching and skin rash. Such reactions occur extremely rarely and are reversible.

The price of the medicine varies from 230 rubles to 450.

The drug "Arbidol"

This medicine is an excellent antiviral immunostimulating agent. The drug is available only in tablet form.

The product is intended for the treatment and prevention of the following pathologies:

influenza, ARVI;
colds complicated by pneumonia, bronchitis;
immunodeficiency states;
herpetic infection;
Chronical bronchitis.

The drug is contraindicated for use in the following cases:

increased sensitivity to the product;
cardiovascular pathologies;
ailments of the liver, kidneys;
age up to 3 years.

Therapy with Arbidol is often very well tolerated by the body. Tablets rarely cause any side effects. Sometimes allergic reactions may occur. But, as a rule, they are observed in isolated cases.

It is not advisable to take this medication during pregnancy. Such a drug can only be prescribed by the attending physician after balancing the predicted benefits and the risk of developing pathologies in the fetus.

The price for this product is on average 164 rubles.

Medicine "Immunal"

This is an excellent remedy with anti-inflammatory, antiviral, and immunostimulating properties. The main component of the medicine is echinacea. Quite often the drug “Immunal” is prescribed for children.

stimulation of immunity for influenza, ARVI, herpes;
frequent colds as a result of weakened immunity;
intoxication of various origins;
psycho-emotional overload;
prevention of ARVI, influenza during epidemics;
complex therapy of bronchitis, pyelonephritis, arthritis.

The drug is prohibited for use in pathologies accompanied by immune disorders:

autoimmune diseases of the bronchopulmonary system, joints;
tuberculosis;
leukemia;
AIDS.

The medicine is not prescribed to babies under one year of age.

You can purchase the drug at almost any pharmacy. The cost of this product varies from 225 to 295 rubles.

First of all, it is necessary to define what is meant by the term “immunotropic drugs”. M.D. Mashkovsky divides drugs that correct immune processes (immunocorrectors) into immunostimulating and immunosuppressive (immunosuppressors). A third group can be distinguished - immunomodulators, that is, substances that have an effect on the immune system depending on its initial state. Such drugs increase low and reduce high indicators of immune status. Thus, according to their effect on the immune system, immunotropic drugs can be divided into immunosuppressors, immunostimulants and immunomodulators.

This section is devoted only to the last two types of drugs and mainly to immunostimulants.

Characteristics of immunomodulators

Preparations of bacterial and fungal origin

Immunomodulator vaccines Vaccines made from opportunistic bacteria not only increase resistance to a specific microbe, but also have a powerful nonspecific immunomodulatory and stimulating effect. This is explained by the presence in their composition of lipopolysaccharides, proteins A, M and other substances of the strongest immune activators that act as adjuvants. An indispensable condition for prescribing immunomodulatory therapy with lipopolysaccharides must be a sufficient level of target cells (i.e., the absolute number of neutrophils, monocytes and lymphocytes).

Bronchomunal ( Broncho - Munal ) - lyophilized bacterial lysate { Str. pneumoniae, H. influence, Str. vindans, Str. pyogenes, moraxella catarrhalts, S. aureus, K. pneumoniae And Kozaenae). Increases the number of T-lymphocytes and IgG, IgM, clgA antibodies, IL-2, TNF; used in the treatment of infectious diseases of the upper respiratory tract (bronchitis, rhinitis, tonsillitis). The capsule contains 0.007 g of lyophilized bacteria, 10 per pack. Prescribe 1 capsule per day for 10 days per month for 3 months. Children are prescribed bronchomunal II, which contains 0.0035 g of bacteria per capsule. Use in the morning on an empty stomach. Dyspeptic symptoms, diarrhea, and epigastric pain are possible.

Ribomunil ( Ribomunyl ) - contains immunomodulatory substances represented by a combination of bacterial ribosomes (Klebsiella pneumoniae - 35 shares Streptococcus pneumoniae - 30 shares, Streptococcus pyogenes - 30 shares, Haemophilia influenzae - 5 lobes) and membrane proteoglycans Kpneumoniae. Prescribed 1 tablet 3 times a day or 3 tablets taken in the morning, on an empty stomach, in the first month - 4 days a week for 3 weeks, and in the next 5 months. - 4 days at the beginning of each month. Forms immunity to infectious agents, provides long-term remission in chronic bronchitis, rhinitis, tonsillitis, otitis.

Multicomponent vaccine (VP-4 - Immunovac) represents antigenic complexes isolated from Staphylococcus, Proteus, Klebsiella pneumoniae and Escherichia coli K-100; induces the production of antibodies to these bacteria in vaccinated individuals. In addition, the drug is a stimulator of nonspecific resistance, increasing the body's resistance to opportunistic bacteria. Correlates the level of T-lymphocytes, enhances the synthesis of IgA and IgG in the blood and slgA in saliva, stimulates the formation of IL-2 and interferon. The vaccine is intended for immunotherapy of patients (age 16-55 years) with chronic inflammatory and obstructive respiratory diseases (chronic bronchitis, chronic obstructive pulmonary disease, infection-related and mixed forms of bronchial asthma). Intranasal administration: 1 day - 1 drop in one nasal passage; Day 2 - 1 drop in each nasal passage; Day 3 - 2 drops in each nasal passage. Starting from the 4th day after the start of immunotherapy, the drug is injected under the skin of the subscapular region 5 times with an interval of 3-5 days, alternately changing the direction of administration. 1st injection - 0.05 ml; 2nd injection 0.1 ml; 3rd injection – 0.2 ml; 4th injection – 0.4 ml; 5th injection – 0.8 ml. When using the vaccine orally, 1-2 days after the end of intranasal administration, the drug is taken orally 5 times with an interval of 3-5 days. 1 dose - 2.0 ml; 2nd dose - 4.0 ml; 3rd dose - 4.0 ml; 5th dose - 4.0 ml.

Staphylococcal vaccine contains a complex of thermostable antigens. It is used to create anti-staphylococcal immunity, as well as to increase general resistance. It is administered subcutaneously in a dose of 0.1-1 ml daily for 5-10 days.

Imudon ( Imudon ) - the tablet contains a lyophilic mixture of bacteria (lactobacillus, streptococcus, enterococcus, staphylococcus, Klebsiella, corynebacterium pseudodiphtheria, fusiform bacteria, candida albicans); used in dentistry for periodontitis, stomatitis, gingitis and other inflammatory processes of the oral mucosa. Prescribe 8 tablets/day (1-2 every 2-3 hours); The tablet is kept in the mouth until completely dissolved.

IRS-19 ( IRS -19) - dosed aerosol for intranasal use (60 doses, 20 ml) contains a lysate of bacteria (diplococcus pneumoniae, streptococci, staphylococci, Neisseria, Klebsiella, Morahella, influenza bacillus, etc.) . Stimulates phagocytosis, increases the level of lysozyme, clgA. Used for rhinitis, pharyngitis, tonsillitis, bronchitis, bronchial asthma with rhinitis, otitis. Make 2-5 injections per day into each nostril until the infection disappears.

Bacterialand yeast substances

Sodium nucleinate The drug in the form of a sodium salt of nucleic acid is obtained by hydrolysis of yeast cells followed by purification. It is an unstable mixture of 5-25 types of nucleotides. It has pluripotent stimulating activity against immune cells: it increases the phagocytic activity of micro- and macrophages, the formation of active acid radicals by these cells, which leads to an increase in the bactericidal effect of phagocytes, and increases titers of antitoxic antibodies. Prescribed orally in tablets in the following doses per 1 dose: children 1 year of life - 0.005-0.01 g, from 2 to 5 years - 0.015-002 g, from 6 to 12 years - 0.05-0 , 1 g. The daily dose consists of two to three single doses, calculated for the patient’s age. Adults receive no more than 0.1 g per dose 4 times a day.

Pyrogenal The drug is obtained from a culture Pseudomonas aeroginosa. Low toxicity, but causes fever, short-term leukopenia, which is then replaced by leukocytosis. The effect on the system of cells of the phagocytic system is especially effective, therefore it is often used in complex therapy of protracted and chronic inflammatory diseases of the respiratory tract and other localizations. It is administered intramuscularly. Injections are not recommended for children under 3 years of age. Children over 3 years old are given a dose of 3 to 25 mcg (5-15 MTD - minimum pyrogenic doses) per injection depending on age, but not more than 250-500 MTD. For adults, the usual dose is 30-150 mg (25-50 MTD) per injection, the maximum is 1000 MTD. The course of therapy includes from 10 to 20 injections, and monitoring of peripheral blood parameters and immune status is necessary.

Pyrogenal test is a test for leukopenic conditions to stimulate the emergency release of immature forms of granulocytes from cellular depots. The drug is administered at a dose of 15 MTD per 1 m2 of body area. Another calculation formula is 0.03 mcg per 1 kg of body weight. Contraindicated during pregnancy, acute fevers, leukopenia of autoimmune origin.

Yeast preparations contain nucleic acids, a complex of natural vitamins and enzymes. They have long been used for bronchitis, furunculosis, long-healing ulcers and wounds, anemia, and during the recovery period after serious illnesses. Add 30-50 ml of warm water to 5-10 g of yeast, grind and leave for 15-20 minutes in a warm place until foam forms. The mixture is shaken and drunk 15-20 minutes before meals 2-3 times a day for 3-4 weeks. The clinical effect appears after a week, the immunological effect - later. To reduce dyspepsia, the drug is diluted with milk or tea.

Synthetic immunomodulators

Lycopid A semi-synthetic drug, it belongs to muramyl dipeptides, similar to bacterial ones. It is a fragment of the bacterial cell wall. Derived from cell wall M. lysodeicticus.

The drug increases the body's overall resistance to pathogenic factors, primarily through the activation of cells of the phagocytic immune system (neutrophils and macrophages). In case of suppressed hematopoiesis, for example, caused by chemotherapy or radiation, the use of licopid leads to the restoration of the number of neutrophils. Lykopid activates T- and B-lymphocytes.

Indications: acute and chronic purulent-inflammatory diseases; acute and chronic respiratory diseases; lesions of the cervix by human papillomavirus; vaginitis; acute and chronic viral infections: ophthalmoherpes, herpetic infections, herpes zoster; pulmonary tuberculosis; trophic ulcers; psoriasis; immunoprophylaxis of colds.

Courses are prescribed depending on the disease. For chronic respiratory tract infections (bronchitis) in the acute stage, 1-2 tablets (1-2 mg) under the tongue - 10 days. For prolonged recurrent infections, 1 tablet (10 mg) once a day for 10 days. Pulmonary tuberculosis: 1 tablet (10 mg) - 1 time under the tongue, 3 cycles of 7 days at intervals of 2 weeks. Herpes (mild forms) - 2 tablets (1 mg x 2) 3 times a day under the tongue for 6 days; for severe cases - 1 tablet (10 mg) 1-2 times a day orally - 6 days. Children are prescribed 1 mg tablets.

Contraindicated during pregnancy. An increase in body temperature up to 38°C, which sometimes occurs after taking the drug, is not a contraindication.

Rheosorbilact - used for detoxification. Apparently, it has an immunomodulatory effect in the treatment of chronic obstructive pulmonary diseases, rheumatism, and intestinal infections. Administer 100-200 ml for adults, 2.5-5 ml/kg for children, intravenously (40-80 drops per minute) every other day.

Dibazol ( Dibazolum ) - vasodilator, antihypertensive agent. The drug has adaptogenic and interferogenic effects, enhances the synthesis of proteins and nucleic acids, the expression of IL-2, and receptors on N-helper cells. Used for acute infections (bacterial and viral). Apparently, the combination of dibazole with licopid should be considered optimal. Prescribed in tablets of 0.02 (single dose - 0.15 g), 1 ampoules; 2; 5 ml 0.5°/, or 1% solution for 7-10 days. For young children - 0.001 g/day, up to one year - 0.003 g/day, preschool age 0.0042 g/day.

Blood pressure should be monitored, especially in adolescent children, in whom dibazole can cause disturbances in the regulation of vascular tone.

Dimexide (dimethyl sulfoxide) Available in 100 ml bottles, it is a liquid with a specific odor, has a unique tissue penetrating ability, pH 11. It has anti-inflammatory, decongestant, bactericidal and immunomodulatory effects. Stimulates phagocytes and lymphocytes. In rheumatology, a 15% solution is used in the form of applications to joints for rheumatoid arthritis. Used for purulent-septic and bronchopulmonary diseases. Course 5-10 applications.

Isoprinasine (groprin azine ) - a mixture of 1 part inosine and 3 parts p-aceto-amidobenzoic acid. Stimulates phagocytic cells and lymphocytes. Stimulates the production of cytokines, IL-2, which significantly changes the functional activity of peripheral blood lymphocytes and their specific immunological functions: differentiation of 0-cells into T-lymphocytes is induced, and the activity of cytotoxic lymphocytes is enhanced. Almost non-toxic and well tolerated by patients. Side effects and complications are not described. Having a pronounced interferonogenic effect, it is used in the treatment of acute and protracted viral infections (herpes infection, measles, hepatitis A and B, etc.). Stimulates mature B cells. Taken orally in the form of tablets (1 tablet 500 mg) at a dose of 50-100 mg per 1 kg of body weight per day. The daily dose is divided into 4-6 doses. Course duration is 5-7 days. Indications: secondary immunodeficiency diseases, especially with herpetic infections.

Imunofan ( Imunofan ) - hexapeptide (arginyl-alpha-aspartyl-lysyl-valine-tyrosyl-arginine) has an immunoregulatory, detoxifying, hepatoprotective effect and causes inactivation of free radicals and peroxide compounds. The effect of the drug develops within 2-3 hours and lasts up to 4 months; normalizes lipid peroxidation, inhibits the synthesis of arachidonic acid with a subsequent decrease in blood cholesterol levels and the production of inflammatory mediators. After 2-3 days, phagocytosis increases. The immunocorrective effect of the drug manifests itself after 7-10 days, enhances the proliferation of T-lymphocytes, increases the production of interleukin-2, the synthesis of antibodies, interferon. Ampoules contain 1 ml of 0.005% solution of the drug (pack of 5 ampoules). Prescribed subcutaneously, intramuscularly daily or every 1-4 days, 1 course of 5-15 injections. For herpes infection, cytomegalovirus, toxoplasmosis, chlamydia, pneumocystosis, 1 injection every two days, course of treatment is 10-15 injections.

Galavit ( Galavit ) - an aminophthalhydroside derivative with anti-inflammatory and immunomodulatory activity. Recommended for secondary immune deficiency and chronic recurrent, sluggish infections of various organs and locations. Prescribed intramuscularly at 200 mg 1 dose, then 100 mg 2-3 times a day until intoxication decreases or inflammation stops. Maintenance course after 2-3 days. Tested for furunculosis, intestinal infections, adnexitis, herpes, cancer chemotherapy; in inhalations for chronic bronchitis.

Polyoxidonium - a new generation synthetic immunomodulator, N-oxidized derivative of polyethylene piperazine, which has a wide spectrum of pharmacological action and high immunostimulating activity. Its predominant influence on the phagocytic component of immunity has been established.

Main pharmacological properties: activation of phagocytes and the digestive ability of macrophages against pathogenic microorganisms; stimulation of cells of the reticuloendothelial system (capture, phagocytose and remove foreign microparticles from the circulating blood); increasing the adhesion of blood leukocytes and their ability to produce reactive oxygen species upon contact with opsonized fragments of microorganisms; stimulation of cooperative T- and B-cell interaction; increasing the body’s natural resistance to infections, normalizing the immune system in case of secondary IDS; antitumor effect. Polyoxidonium is prescribed to patients once a day intramuscularly, using doses from 6 to 12 mg. The course of administration of polyoxidonium is from 5 to 7 injections, every other day or according to the scheme: 1-2-5-8-11-14 days of drug administration.

Methyluracil stimulates leukopoiesis, enhances cell proliferation and differentiation, and antibody production. Prescribed orally for 1 dose: children from 1-3 years old - 0.08 g, from 3-8 years - 0.1 - 0.2 g; from 8-12 years and adults - 0.3-0.5 g. Patients are given 2-3 single doses per day. The course lasts 2-3 weeks. For secondary immunological deficiency, it is used in patients with moderate cytopenic conditions.

Theophylline stimulates suppressor T cells at a dose of 0.15 mg 3 times a day for 3 weeks. In this case, not only a decrease in the number of B cells is noted, but also a suppression of their functional activity. Can be used in the treatment of autoimmune diseases and autoimmune syndrome in immunodeficiency. However, the main purpose of the drug is the treatment of bronchial asthma, as it has a bronchodilator effect.

Famotidine - blockers of H2 histamine receptors, inhibit T-suppressors, stimulate T-helpers, the expression of IL-2 receptors and the synthesis of immunoglobulins.

Interferon inducers stimulate the production of endogenous interferon.

Amiksin - stimulates the formation of α, β, and gamma interferons, enhances antibody formation, has an antibacterial and antiviral effect. Used for the treatment of hepatitis A and enteroviral infections (1 tablet - 0.125 g for adults and 0.06 - for children for 2 days , then take a break of 4-5 days, the course of treatment is 2-3 weeks), for the prevention of viral infections (flu, acute respiratory infections, acute respiratory viral infections) - 1 tablet. Once a week, 3-4 weeks. Contraindicated in pregnancy, liver and kidney diseases.

Arbidol - antiviral drug. It has an inhibitory effect on influenza A and B viruses. It has interferon-inducing activity and stimulates humoral and cellular immune responses. Release form: tablets of 0.1 g. For the treatment of viral infections, 0.1 g is prescribed three times a day before meals for 3-5 days, then 0.1 g once a week for 3-4 weeks. . Children 6-12 years old: 0.1 g every 3-4 days for 3 weeks as a preventive measure during a flu epidemic. For treatment: children – 0.1 g 3-4 times a day for 3-5 days. Contraindicated in patients with cardiovascular diseases, liver and kidney diseases.

Neovir - induces the synthesis of alpha-interferon, activates stem cells, NK cells, T-lymphocytes, macrophages, reduces the level of TNF-α. In the acute period of herpes infection, 3 injections of 250 mg are prescribed with an interval of 16-24 hours and another 3 injections with an interval of 48 hours. In the inter-relapse period, 1 injection per week at a dose of 250 mg for a month. For urogenital chlamydia, 5-7 injections of 250 mg with an interval of 48 hours. Antibiotics are prescribed on the day of the second injection. Available as a sterile solution for injection in 2 ml ampoules containing 250 mg of active substance in 2 ml of physiologically compatible buffer. Pack of 5 ampoules.

Cycloferon - 12.5% solution for injection - 2 ml, tablets 0.15 g, 5% ointment 5 ml. Stimulates the formation of α, β, and γ-interferons (up to 80 U/ml), increases the level of CD4+ and CD4+ T-lymphocytes in HIV infection. Recommended for herpes, cytomegalovirus infection, hepatitis, HIV infection, multiple sclerosis, gastric ulcer, rheumatoid arthritis. A single dose of 0.25-0.5 g IM or IV on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, 29. Children: 6-10 mg/kg/day - IV or IM. Tablets 0.3 - 0.6 g 1 time per day. Prescribed for influenza and respiratory infections; ointment - for herpes, vaginitis, urethritis.

Kagocel - a synthetic preparation based on carboxymethylcellulose and polyphenol - gossypol. Induces the synthesis of α and β-interferons. After a single dose, they are produced within a week. Tablets 12 mg. For the treatment of influenza and ARVI, adults are prescribed 2 tablets 3 times a day in the first two days, and one tablet 3 times a day in the next two days. A total of 18 tablets per course, course duration - 4 days. Prevention of respiratory viral infections in adults is carried out in 7-day cycles: two days - 2 tablets once a day, 5 days break, then repeat the cycle. The duration of the preventive course is from one week to several months. For the treatment of herpes in adults, 2 tablets are prescribed 3 times a day for 5 days. A total of 30 tablets per course, course duration - 5 days. For the treatment of influenza and ARVI, children over 6 years of age are prescribed 1 tablet 3 times a day in the first two days, and one tablet 2 times a day in the next two days. A total of 10 tablets per course, course duration - 4 days.

Immunofan And dibazole - (see above) are also interferonogens.

Dipyridamole (chimes) - a vasodilator drug, used 0.05 g 2 times a day at an interval of 2 hours once a week increases the level of interferon gamma, relieves viral infections.

Anaferon - contains low doses of antibodies to interferon gamma, therefore it has immunomodulatory properties. Used for viral infections of the upper respiratory tract (flu, ARVI) 5-8 tablets on the 1st day and 3 on the 2nd - 5th day. For prevention - 0.3 g - 1 tablet for 1-3 months.

Preparations obtained from cells and organs of the immune system

Thymic peptides and hormones The most important feature of thymic peptides (derived from epithelial, stromal cells, Hassall bodies, thymocytes, etc.) as hormones is the short duration and short-distance of their action on target cells. This largely determines therapeutic tactics. Medicinal preparations are obtained in various ways from animal thymus extracts.

Thymic peptides have a common property for the entire group to enhance the differentiation of cells of the lymphoid system, changing not only the functional activity of lymphocytes, but also causing the secretion of cytokines, such as IL-2.

Indications for prescribing drugs in this group are clinical and laboratory signs of T-cell immunity deficiency: infectious or other syndromes associated with immunological deficiency; lymphopenia, decrease in the absolute number of T-lymphocytes, CD4 + /CD8 + lymphocyte ratio index, proliferative response to mitogens, depression of delayed-type hypersensitivity reactions in skin tests, etc. .

Thymic insufficiency may be acute And chronic. Acute thymic insufficiency is formed during intoxication, physical or psycho-emotional stress, against the background of severe acute infectious processes. Chronic characterizes T-cell and combined forms of immunodeficiency. Thymic insufficiency should not be corrected by immunostimulating effects; it should be replaced by preparations of thymic peptide hormones.

Replacement therapy for acute thymic failure usually requires a short course of saturation of thymic peptides against the background of symptomatic therapy. Chronic thymic failure is replaced by regular courses of thymic peptides. Typically, the first 3-7 days the drugs are administered in a saturation mode, and then continued as maintenance therapy.

Congenital forms of immunological deficiency of the T-cell type almost impossible to correct by thymic factors, usually due to genetically determined defects in target cells or the production of mediators (for example, IL-2 and IL-3). Acquired immunodeficiencies are well corrected by thymic factors if the genesis of immunodeficiency is due to thymic insufficiency and, as a consequence, immaturity of T cells. However, thymic peptides do not correct other defects of T-lymphocytes (enzyme, etc.).

Timalin - complex of calf thymus peptides. Lyophilized powder in 10 mg bottles is dissolved in 1-2 ml of isotonic sodium chloride solution. Administered intramuscularly to adults: 5-20 mg (30-100 mg per course), to children up to 1 g: 1 mg; 4-6 years 2-3 mg; 4-14 years - 3.5 mg for 3-10 days. Recommended for acute and chronic viral and bacterial infections, burns, ulcers, infectious bronchial asthma; diseases associated with immunodeficiency.

Taktivin - complex of calf thymus polypeptides. Available in bottles of 1 ml - 0.01% solution. For chronic nonspecific lung diseases, the optimal dose of tactivin is 1-2 mcg/kg. The drug is administered 1 ml (100 mcg) subcutaneously for 5 days, then once a week for 1 month. Subsequently, 5-day monthly refresher courses are conducted. Recommended for purulent-septic processes, lymphocytic leukemia, ophthalmic herpes, tumors, psoriasis, multiple sclerosis and diseases associated with immunodeficiency.

Timostimulin - a complex of bovine thymus polypeptides, administered intramuscularly at a dose of 1 mg per 1 kg of body weight for 7 days, then 2-3 times a week. This mode of administration was used in the treatment of combined forms of primary immunological deficiency. The best clinical effect is observed in patients with defects in the functional activity of cellular immunity effectors. Allergic reactions to the drug are possible.

Blood and immunoglobulin products Passive, replacement immunotherapy includes a group of methods based on the introduction of ready-made SI factors to the patient from the outside. Three types of human immunoglobulin preparations are used in clinical practice: native plasma, immunoglobulin for intramuscular administration and immunoglobulin for intravenous administration.

Autohemotransfusion serves as an alternative to allogeneic blood transfusion. For planned operations, it is recommended (Shander, 1999) to prepare autologous blood in advance with the administration of erythropoietin once a week at a dose of 400 units/kg for 3 weeks, as well as recombinant stimulators of leukopoiesis (GM-CSF), IL-11, which stimulates thrombocytopoiesis.

Leukocyte mass used as a means of replacement therapy for immunodeficiency states of the phagocytic system. The dose of leukomass is 3-5 ml per 1 kg of body weight.

Stem cells - autologous and allogeneic, bone marrow and isolated from blood, capable of restoring the functions of organs and tissues through differentiation into mature cells.

Native blood plasma (liquid, frozen) contains at least 6 g of total protein per 100 ml, incl. albumin 50% (40-45 g/l), alpha 1-globulin - 45%; alpha 2-globulin - 8.5% (9-10 g/l), beta globulin 12% (11-12 g/l), gamma globulin - 18% (12-15 n/l). It may contain cytokines, ABO antigens, and soluble receptors. Available in bottles or plastic bags of 50-250 ml. Native plasma should be used on the day of its production (no later than 2-3 hours after separation from the blood). Frozen plasma can be stored at -25°C or below for 90 days. At a temperature of -10°C, the shelf life is up to 30 days.

Plasma transfusion is carried out taking into account blood group compatibility (ABO). At the beginning of the transfusion, it is necessary to conduct a biological test and, if signs of a reaction are detected, stop the transfusion.

Dry (lyophilized) plasma due to a decrease in therapeutic usefulness due to denaturation of some unstable protein components, a significant content of polymeric and aggregated IgG, and high pyrogenicity, it is not advisable to use it for immunotherapy of antibody deficiency syndromes.

Human normal immunoglobulin intramuscular The preparations are made from a mixture of more than 1000 donor blood sera, due to which they contain a wide range of antibodies of different specificities, reflecting the state of collective immunity of the donor contingent. Prescribed for the prevention of infectious diseases: hepatitis, measles, whooping cough, meningococcal infection, polio. However, they are of little use for replacement therapy of antibody deficiency syndromes in primary and secondary immunodeficiencies. Most immunoglobulin is destroyed at the site of administration, which, at best, may produce beneficial immunostimulation.

The production of hyperimmune intramuscular immunoglobulins, such as anti-staphylococcal, anti-influenza, anti-tetanus, anti-botulinum, used for specific immunotherapy, has been established.

Intravenous immunoglobulins (IVIG) are safe in terms of transmitting viral infections, contain a sufficient amount of IgG3, responsible for neutralizing viruses, by the activity of the Fc fragment. Indications for use:

1. Diseases for which the effect of IVIG has been convincingly proven:

- Pprimary immunodeficiencies(X-linked agammaglobulinemia; common variable immunodeficiency; transient hypogammaglobulinemia of children; immunodeficiency with hyperglobulinemia M; deficiency of immunoglobulin G subclasses; deficiency of antibodies with normal levels of immunoglobulins; severe combined immunodeficiencies of all types; Wiskott-Aldrich syndrome; ataxia-telangiectasia; dwarfism with selectively short limbs; X-linked lymphoproliferative syndrome.

- secondary immunodeficiencies: hypogammaglobulinemia; prevention of infections in chronic lymphocytic leukemia; prevention of cytomegalovirus infection during allogeneic transplantation of bone marrow and other organs; rejection syndrome during allogeneic bone marrow transplantation; Kawasaki disease; AIDS in pediatric practice; Gillien Baret's disease; chronic demyelinating inflammatory polyneuropathies; acute and chronic immune thrombocytopenic purpura, including in children and associated with HIV infection; autoimmune neuropenia.

2. Diseases for which IVIG is likely to be effective: malignant neoplasms with antibody deficiency; prevention of infections in myeloma; enteropathy accompanied by protein loss and hypogammaglobulinemia; nephrotic syndrome with hypogammaglobulinemia; neonatal sepsis; myasthenia gravis; bullous pemphigoid; coagulopathy with the presence of an inhibitor to factor VIII; autoimmune hemolytic anemia; neonatal auto- or isoimmune thrombocytopenic purpura; post-infectious thrombocytopenic purpura; anticardiolipin antibody syndrome; multifocal neuropathies; hemolytic-uremic syndrome; systemic juvenile arthritis, spontaneous abortion (antiphospholipin syndrome); Henoch-Schönlein disease; severe IgA neuropathy; steroid-dependent bronchial asthma; chronic sinusitis; viral infections (Epstein-Barr, respiratory syncytial, parvo-, adeno-, cytomegalovirus, etc.); bacterial infections; multiple sclerosis; hemolytic anemia; viral gastritis; Evans syndrome.

4. Diseases for which the use of IVIG may be effective intractable seizures; systemic lupus erythematosus; dermatomyositis, eczema; rheumatoid arthritis, burn disease; Duchenne muscular atrophy; diabetes; thrombocytopenic purpura associated with heparin administration; necrotizing enterocolitis; retinopathy; Crohn's disease; multiple trauma, recurrent otitis media; psoriasis; peritonitis; meningitis; meningoencephalitis

Features of the clinical use of IVIG.

There are several options for the therapeutic and prophylactic use of immunoglobulins: replacement therapy for immunodeficiencies complicated by infection; immunotherapy for patients with severe infection (sepsis); suppressive IT in autoallergic and allergic diseases.

Hypogammaglobulinemia usually occurs in children with active bacterial infections. In such cases, immunotherapy should be carried out in a saturation regimen, simultaneously with active antimicrobial chemotherapy. Transfusion of native (fresh or cryopreserved) plasma is carried out in a single dose of 15-20 ml/kg body weight.

IVIG is administered at a daily dose of 400 mg/kg intravenously or infusionally at 1 ml/kg/hour for premature infants and 4-5 ml/kg/hour for full-term infants. For premature infants weighing less than 1500 g and an IgG level of 3 g/l or lower, IVIG is administered to prevent infections. For immunodeficiencies with low levels of IgG in the blood, IVIG is administered until the concentration of IgG in the blood is not lower than 4-6 g/l. For severe purulent-inflammatory diseases, they are administered 3-5 injections daily or every other day up to 1-2.5 g/kg. In the initial period, the intervals between infusions can be 1-2 days, in the end up to 7 days. 4 - 5 injections are sufficient, so that in 2 - 3 weeks the patient receives on average 60-80 ml of plasma or 0.8-1.0 g of IVIG per 1 kg of body weight. No more than 100 ml of plasma or 1.2 g of IVIG per 1 kg of patient body weight is transfused per month.

After relieving exacerbations of infectious manifestations in a child with hypogammaglobulinemia, as well as achieving levels of at least 400-600 mg/dL, one should switch to a maintenance immunotherapy regimen. Clinically effective preservation of the child from exacerbation of foci of infection correlates with pre-transfusion levels above 200 mg/dl (correspondingly, post-transfusion levels on the day after plasma transfusion are above 400 mg/dl). This requires monthly administration of 15-20 ml/kg body weight of native plasma or 0.3-0.4 g/kg IVIG. To obtain the best clinical effect, long-term and regular replacement therapy is necessary. Over the course of 3-6 months after completion of the course of immunotherapy, a gradual increase in the completeness of sanitation of foci of chronic infection is observed. This effect is maximally manifested after 6-12 months of continuous replacement immunotherapy.

Intraglobin - VIG contains 50 mg of IgG and about 2.5 mg of IgA in 1 ml; it is used for immunodeficiencies, infections, and autoimmune diseases.

Pentaglobin - VIG enriched with IgM and contains: IgM - 6 mg, IgG - 38 mg, IgA -6 mg in 1 ml. Used for sepsis, other infections, immunodeficiency: for newborns 1 ml/kg/hour, 5 ml/kg daily for 3 days; adults 0.4 ml/kg/hour, then 0.4 ml/kg/hour, then continuously 0.2 ml/kg up to 15 ml/kg/hour for 72 hours - 5 ml/kg 3 days, if necessary - repeat course.

Octagam - VIG contains 50 mg of plasma proteins per 1 ml, of which 95% IgG; less than 100 µg IgA, and less than 100 µg IgM. Close to native plasma IgG, all IgG subclasses are present. Indications: congenital agammaglobulinemia, variable and combined immunodeficiencies, thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation.

For immunodeficiency, it is administered until the level of IgG in the blood plasma is 4-6 g/l. Initial dose 400-800 mg/kg, followed by 200 mg/kg every 3 weeks. To achieve an IgG level of 6 g/l, it is necessary to administer 200-800 mg/kg per month. For control, the level of IgG in the blood is determined.

For the treatment and prevention of infections, IVIG doses depend on the type of infectious process. As a rule, it is administered as early as possible. For cytomegalovirus (CMV) infection, the dose should be 500 mg/kg weekly for 12 weeks because the half-life of the IgG3 subclass responsible for neutralizing the virus is 7 days, and the infection manifests clinically between 4-12 weeks after infection. At the same time, synergistically acting antiviral drugs are prescribed.

For the prevention of neonatal sepsis in premature infants weighing from 500 to 1750 grams, it is recommended to administer from 500 to 900 mg/kg/day IgG to maintain its concentration of at least 800 mg/kg under the control of the level of IgG in the blood. The increase in IgG levels persists for an average of 8-11 days after administration. Administration of IgG to pregnant women after 32 weeks reduced the risk of infection in newborns.

IVIG drugs are also used to treat sepsis, especially in combination with antibiotics. The recommended blood level is more than 800 mg/kg.

After allogeneic bone marrow transplantation, IVIG is administered weekly for 3 months and then 500 mg/kg every 3 weeks for 9 months to prevent CMV and other infections.

When treating autoimmune diseases, doses are 250-1000 mg/kg for 2-5 days every 3 weeks. Children with autoimmune thrombocytopenic purpura are administered 400 mg/kg for 2 days, adults - 1 g/kg for 2 or 5 days.

The mechanism of action of immunoglobulins depends on the conditionFc-receptors of leukocytes: by contacting them, immunoglobulins enhance functions during infection, and, conversely, inhibit them during allergies.

Anti-Rhesus immunoglobulin suppresses the synthesis of antibodies against a Rh-positive fetus in a Rh-negative woman by feedback type.

Mechanism of actionIgGconsists of a specific and nonspecific effect. Specific is associated with the action of a small amount of always present antibodies. Nonspecific - with an immunomodulatory effect. Both effects are usually mediated throughFc-leukocyte receptors. ContactingFc-receptors of leukocytes, immunoglobulins activate them, in particular phagocytosis. If there are antibodies among the immunoglobulin molecules, they can opsonize bacteria or neutralize viruses.

Novikov D.K. and Novikova V.I. (2004) developed a method for predicting the effectiveness of immunoglobulin drugs. It was found that the therapeutic effect of immunoglobulin drugs depended on the presence of Fc receptors on the leukocytes of patients. The method involves determining in the blood of patients before treatment the number of leukocytes carrying receptors for Fc fragments of immunoglobulins and the ability of leukocytes to be sensitized by antistaphylococcal immunodrugs. In the presence of 8% or more lymphocytes and 10% or more granulocytes in an amount of more than 100 in 1 μl of blood that have Fc receptors, and a positive reaction to the transfer of sensitization, the effectiveness of immunotherapy is predicted.

The results of the transfer of sensitization to lymphocytes by the immunodrug are assessed in the reaction of suppression of leukocyte migration, using antigens corresponding to the antibodies in the antiserum, for example, staphylococcal antigens. If staphylococcal antigens suppress the migration of leukocytes treated with antistaphylococcal plasma, but do not suppress the migration of leukocytes treated with normal plasma, the reaction is considered positive.

The proposed method makes it possible to predict the effectiveness of both specific (when using immune drugs) and nonspecific (for Fc receptors) immunotherapy with immunoglobulins.

Monoclonal antibodies mice against human lymphocytes and cytokines are used to suppress autoimmune reactions and transplantation immunity. The following are some uses of monoclonal antibodies:

Antibodies against CD20 B cells for immunosuppression ( Mabthera )

Antibodies against interleukin 2 receptors - in case of threat of kidney allograft rejection;

Antibodies against IgE - for severe allergic reactions ( Xolair ).

Bone marrow, leukocyte and spleen preparations

Myelopid obtained from the culture of porcine bone marrow cells. It contains immunomodulators of bone marrow origin - myelopeptides. Myelopid stimulates antitumor immunity, phagocytosis, antibody-producing cells, proliferation of granulocytes and macrophages in the bone marrow. Myelopid is used in the treatment of septic, protracted and chronic infectious diseases of a bacterial nature, secondary immunodeficiencies, since it has the ability to enhance the synthesis of antibodies in the presence of antigens. Myelopid (5 mg bottle) is administered intramuscularly daily or every other day. Single dose 0.04-0.06 mg/kg. The course of therapy consists of 3-10 injections performed every other day.

Leukocyte transfer factor(“transfer factor”) a group of biologically active substances extracted from leukocytes of healthy or immunized donors using repeated sequential freezing and thawing. Transfer factors enhance delayed-type hypersensitivity to specific antigens. The drug prevents the development of immunological tolerance, enhances the differentiation of T cells, neutrophil chemotaxis, the formation of interferons, and the synthesis of immunoglobulins (mainly class M). A single dose for adults is 1-3 units of dry matter. Used in the treatment of primary immunodeficiencies, especially the macrophage type and the treatment of secondary immunodeficiencies of the lymphoid type (with defects in the differentiation and proliferation of T cells, impaired chemotaxis and antigen presentation).

Cytokines- a group of biologically active glycopeptide mediators secreted by immunocompetent cells, as well as fibroblasts, endothelial and epithelial cells. Main directions of cytokine therapy:

Inhibition of the production of inflammatory cytokines (IL-1, TNF-α) using anti-inflammatory drugs and monoclonal antibodies;

Correction of insufficient immunoreactivity with cytokines (IL-2, IL-1 drugs, interferons);

Enhancement of the immunostimulating effect of vaccines by cytokines;

Stimulation of antitumor immunity by cytokines.

Betaleikin - recombinant IL-lβ, available in ampoules of 0.001; 0.005 or 0.0005 mg (5 ampoules). Stimulates leukopoiesis during leukopenia caused by cytostatics and radiation, and the differentiation of immunocompetent cells. Used in oncology, for postoperative complications, protracted, purulent-septic infections. Administered intravenously at a dose of 5 ng/kg for immunostimulation; 15-20 ng/kg to stimulate leukopoiesis daily with 500 ml of 0.9% sodium chloride solution for 1 - 2 hours. Course - 5 infusions.

Ronkoleikin - recombinant IL-2. Indications: signs of immunodeficiency, purulent-inflammatory diseases, sepsis, peritonitis, abscesses and cellulitis, pyoderma, tuberculosis, hepatitis, AIDS, cancer. For sepsis, 0.25 - 1 mg (25,000 - 1,000,000 IU) is administered in 400 ml of 0.9% sodium chloride solution intravenously at a rate of 1-2 ml/min for 4-6 hours, for oncological diseases - 1-2 million units 2-5 times at intervals of 1-3 days, 25,000 IU in 5 ml of saline are administered into the maxillary or frontal sinuses for sinusitis; installations in the urethra for chlamydia daily 50,000 IU (14-20 days); orally for yersineosis and diarrhea, 500,000 - 2,500,000 in 15-30 ml of distilled water on an empty stomach daily for 2-3 days. Ampoules of 0.5 mg (500,000 ME), 1 mg (1,000,000 ME).

Neupogen (filgrastim) - recombinant granulocyte colony-stimulating factor (G-CSF) stimulates the formation of functionally active neutrophils and partially monocytes within the first 24 hours after administration, activates hematopoiesis (for collection of autologous blood and bone marrow for transplantation). Used for chemotherapeutic neutropenia, for the prevention of infections at a dose of 5 mcg/kg/day intravenously or subcutaneously 24 hours after the treatment cycle for 10-14 days. For congenital neutropenia, 12 mcg/kg per day subcutaneously daily.

Leucomax (molgramostim) - recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Used for leukopenia at a dose of 1-10 mcg/kg/day, subcutaneously according to indications.

Granocyte (lenograstim) - granulocyte colony-stimulating factor, stimulates the proliferation of granulocyte precursors, neutrophils. Used for neutropenia at 2-10 mcg/kg/day for 6 days.

Leukinferon - is a complex of cytokines of the first phase of the immune response and includes IFN-α, IL-1, IL-6, IL-12, TNF-α, MIF. For bacterial infections, the course of treatment should be intensive (every other day, one amp., IM) and only when the immune system is restored, supportive (2 times a week, 1 amp., IM).

Interferons The classification of interferons according to their origin is presented in Table 1.

Table 1. Classification of interferons

Source of interferon	A drug	Target cell
Leukocytes	α-interferon (egiferon, welferon)
Fibroblasts	β-interferon (fibloferen, betaferon)	Virus-infected cell, macrophages, NK, epithelium	Antiviral, antiproliferative
T, B, or NK cells	γ-interferon (gamma-feron, immunoferon)	T cells and NK	Enhanced cytotoxicity, antiviral
Biotechnology	recombinant α 2 -interferon (reaferon, intron A)
Biotechnology	Ω-interferon		Antiviral, antitumor

The mechanism of the immunomodulatory action of interferons is realized through increased expression of receptors on cell membranes and through involvement in differentiation. They activate NK, macrophages, granulocytes, and inhibit tumor cells. The effects of different interferons vary. Type I interferons - α and β - stimulate expression on MHC class I cells, and also activate macrophages and fibroblasts. Interferon-gamma type II enhances the functions of macrophages, the expression of MHC class II, the cytotoxicity of NK and T-killers. The biological significance of interferons is not limited only to a pronounced antiviral effect; they exhibit antibacterial and immunomodulatory activity.

The interferon status of an immunocompetent person is normally determined by trace amounts of these glycoproteins in the blood (< 4 МЕ/мл) и на слизистых оболочках, но лейкоциты здоровых людей при антигенном раздражении обладают выраженной способностью синтезировать интерфероны. При хронических вирусных заболеваниях (герпес, гепатит и др.) способность к выработке интерферонов у больных снижена. Наблюдается синдром дефецита интерферона. В то же время у детей в случаях первичных иммунодефицитов лимфоидного типа интерферонная функция лейкоцитов сохранена. При антигенном стимуле в норме вырабатываются все типы интерферонов, однако наибольшее значение для местного противовирусного иммунного статуса имеет титр α-интерферона.

Interferons in doses up to 2 millionM.E.have an immunostimulating effect, and their high doses (10 millionM.E.) cause immunosuppression.

It must be remembered that all interferon drugs can cause fever, flu-like syndrome, neutropenia and thrombocytopenia, alopecia, dermatitis, liver and kidney dysfunction and a number of other complications.

Leukocyte α-interferon (egiferon, valferon) used as a prophylactic drug in the form of local applications to the mucous membrane during epidemic periods and in the treatment of the early stages of acute respiratory and other viral diseases. For viral rhinitis, it is necessary to administer intranasally a fairly large dose (3x10 b ME) 3 times a day in the early period of the disease. The drug is quickly eliminated by mucus and inactivated by its enzymes. Using it for more than a week may cause increased inflammation. Interferon eye drops are used for viral eye infections.

Interferon-β (betaferon) used to treat multiple sclerosis, inhibits the replication of viruses in brain tissue, activates suppressors of the immune response.

Human immune γ-interferon (gammaferon) has cytotoxic effects, modulates the activity of T-lymphocytes and activates B-cells. In this case, the drug can cause inhibition of antibody formation, phagocytosis and modify the response of lymphocytes. The effect of γ-interferon on T cells lasts 4 weeks. Used for psoriasis, HIV infection, atopic dermatitis, tumors.

Doses of interferon preparations for parenteral administration are selected individually: from several thousand units per 1 kg of body weight to several million units per 1 injection. Course 3-10 injections. Adverse reactions: flu-like syndrome.

Recombinant interferon alpha-2β (intron A) prescribed for the following diseases:

multiple myeloma– s/c 3 r. per week, 2 x10 5 IU/m2.

Galoshi's sarcoma- 50 x 10 5 IU/m 2 subcutaneously daily for 5 days, followed by a break of 9 days, after which the course is repeated;

malignant melanoma- 10 x 10 6 IU subcutaneously 3 times a week every other day for at least 2 months;

hairy cell leukemia- s/c 2 x 10 b IU/m 2 3 r. per week 1-2 months;

papilomatosis, viral hepatitis- initial dose 3 x 10 b IU/m 3 times a week for 6 months in the first case (after surgical removal of papillomas) and 3-4 months in the second case.

Laferon (laferobiot) recombinant alpha-2beta interferon is used in the treatment of adults and children with: acute and chronic viral hepatitis; acute viral and viral-bacterial diseases, rhino- and coronavirus, parainfluenza infections, ARVI; with meningoencephalitis; for herpetic diseases: herpes zoster, skin lesions, genitals, keratitis; acute and chronic septic diseases (sepsis, septicemia, osteomyelitis, destructive pneumonia, purulent mediastenitis); multiple sclerosis (injections for at least one year); cancer of the kidneys, breast, ovary, bladder, melanoma (including in disiminated form); hematological malignancies: hairy cell leukemia; chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoblastic lymphosarcoma, T-cell lymphoma, multiple myeloma, Kaposi's sarcoma; as a remedy that relieves intoxication during radiation and chemotherapy of cancer patients. Laferon is available in: 100 thousand IU, 1 million IU, 3 million IU, 5 million IU, 6 million IU, 9 million IU and 18 million IU. Prescribed for: herpes zoster inject along the nerve near the rash with 2-3 million IU in 5 ml saline. solution and application of laferon mixed with LA-KOS cosmetic emulsion (or baby cream) to the papules in a ratio of 1 million IU of laferon per 1-2 cm 3 of cream; acute viral hepatitis B IM 1 - 2 million IU 2 r. per day 10 days; X chronic viral hepatitis B IM 5 million IU 3 r. per week for 4-6 weeks (in case of a hyperthermic reaction, take 0.5 g of paracetamol 20-30 minutes before Laferon administration; if necessary, repeat the antipyretics 2-3 hours after Laferon injection); at x chronic viral hepatitis C IM at a dose of 3 million IU 3 r. per week 6 months; for ARVI and influenza : IM 1-2 million IU 1-2 r. per day along with intranasal administration (1 million IU diluted in 5 ml of saline solution, pour 0.4-0.5 ml into each nasal passage 3-6 times a day, warm the solution to 30- 35°С); with post-influenza meningoencephalitis administer 2-3 million IU intravenously 2 times. per day (under the protection of antipyretics); for sepsis intramuscular (drip in saline solution) administration at a dose of 5 million IU for 5 days or more; at d isplasia of the cervical epithelium, papilloma of viral and herpetic origin, for chlamydia IM 3 million IU for 10 days and locally: 1 million IU of Laferon mixed with 3-5 cm 3 of LA-KOS cosmetic emulsion (or baby cream), apply using an applicator to the cervix every day (preferably before bedtime); at k eratitis, keratoconjunctivitis, keratouveitis parabulbar 0.25-0.5 million IU 3 - 10 days and Laferon in instillations: 250-500 thousand IU per 1 ml saline. solution 8-10 times a day; for warts IM 1 million IU for 30 days; for multiple sclerosis IM 1 million IU 2-3 times a day for 10 days, then 1 million IU 2-3 times a week for 6 months; for cancer of various locations IM 3 million IU 5 days before surgery, then courses of 3 million IU 10 days after 1.5-2 months; with primary limited melanoblastoma endolymphatic administration of 6 million IU/m 2 in combination with cytostatics, maintenance therapy with weekly courses: 2 million IU/m 2 of Laferon every other day, 4 times (course - 8 million IU/m 2) monthly; for multiple myeloma – intramuscularly daily at a dose of 7 million IU/m 2 for 10 days (course - 70 million IU/m 2) after a course of chemotherapy and gamma therapy, maintenance therapy with weekly courses at a dose of 2 million IU/m 2 IM, 4 injections every other day (course - 8 million IU/m2), for 6 months, interval between courses 4 weeks; With Kaposi's arcoma IM 3 million IU/m2 10 days after cytostatic therapy, maintenance therapy with weekly courses, subcutaneous injection 2 million IU/m2 4 times every other day (course - 8 million IU/m2), 6 courses with at intervals of 4 weeks; b asal cell carcinoma subcutaneous injection into the tumor area of 3 million IU in 1-2 ml of water for injection, 10 days, repeat course after 5-6 weeks.

Roferon-A - recombinant interferon - alpha 2a is administered intramuscularly (up to 36 million IU) or subcutaneously (up to 18 million IU). For hairy cell leukemia - 3 million IU/day IM for 16-24 weeks; multiple myeloma - 3 million IU 3 times a week intramuscularly; Kaloshi's sarcoma and renal cell carcinoma - 18-36 million IU per day; viral hepatitis B - 4.5 million IU intramuscularly 3 times a week for 6 months.

Viferon - recombinant interferon alpha-2β is used in the form of suppositories (150 thousand ME, 500 thousand ME, 1 million ME), ointment (40 thousand ME per 1 g). Prescribed for infectious and inflammatory diseases (ARVI, pneumonia, meningitis, sepsis, etc.), for hepatitis, for herpes of the skin and mucous membranes - 1 time per day or every other day in suppositories; for herpes - additionally lubricate the affected areas of the skin with ointment 2-3 times a day. For children, suppositories of 150 thousand ME 3 times a day every 8 hours for 5 days. For hepatitis - 500 thousand ME.

Reaferon (interal) recombinant interferon α2 is prescribed for hepaitis B and viral meningoencephalitis intramuscularly at 1-2x10 b ME 2 times a day for 5-10 days, then the dose is reduced. For influenza and measles, intranasal-Co can be used; for genital herpes - ointment (0.5x10 6 IU/g), herpes zoster - intramuscularly 1x10 6 IU per day for 3-10 days. Also used to treat tumors.

Biostimulants of various origins Many signals connecting the central nervous system and the immune system are transmitted by biologically active substances that perform the functions of neutrotransmitters and neuromodulators in the central nervous system, and the functions of hormones in peripheral tissues. These include: hormones, biogenic amines and peptides. Neuroregulatory biological mediators and hormones affect the differentiation of lymphocytes and their functional activity. For example, the adenohypophysis secretes such immunotropic mediators as somatotropin, adreno-corticotropic hormone, gonadotropic hormones, a group of thyroid-stimulating hormones, as well as a special hormone - thymocyte growth factor.

Heparin - mucopolysaccharide with M.M. 16-20 KDa, stimulates hematopoiesis, enhances the release of leukocytes from the bone marrow depot and increases the functional activity of cells, enhances the proliferation of lymphocytes in the lymph nodes, increases the resistance of peripheral blood erythrocytes to hemolysis. In doses of 5 - 10 thousand units it has a fibrinolytic, platelet disaggregating and weak immunosuppressive effect, enhances the effect of steroids and cytostatics. When administered intradermally to patients at several points in small doses from 200 to 500 units, it has an immunoregulatory effect - it normalizes the reduced level of lymphocytes, their subpopulation spectrum; At the same time, it has a stimulating effect on neutrophils.

Vitamins Under the influence of vitamins, the activity of biochemical processes in cells, including immunological ones, changes. Some forms of immunological deficiency are associated with a deficiency of certain vitamins. An example would be the primary form of phagocytosis defect - Chediak-Higashi syndrome. In case of echo disease, taking vitamin C at a dose of 1 gram per day for several weeks activates the enzymatic redox systems of phagocytes (neutrophils and macrophages) to the stage of compensation of their bactericidal function.

Ascorbic acid normalizes the activity of T-lymphocytes and neutrophils in patients with initially reduced levels. However, high doses (10 g) cause immunosuppression.

Vitamin E - (tocopherol acetate, α-tocopherol) found in sunflower, corn, soybean, sea buckthorn oil, eggs, milk, meat. It has antioxidant and immunostimulating properties and is used for muscular dystrophies, sexual dysfunction, and chemotherapy. Prescribed orally and intramuscularly at 0.05-0.1 g per day for 1-2 months. Administration of vitamin E in a daily dose of 300 IU orally for 6-7 days increases the number of leukocytes, T- and B-lymphocytes. In combination with selenium, vitamin E increased the number of antibody-forming cells. It is believed that vitamin E changes the activity of lipo- and cyclooxygenases, enhances the production of IL-2 and immunity, and inhibits tumor growth. Tocopherol at a dose of 500 mg daily normalized immune status indicators.

Zinc acetate (10 mg 2 times a day, 5 mg up to 1 month) is a stimulator of antibody formation and delayed-type hypersensitivity. Zinc thymulin is considered one of the main thymus hormones. Zinc preparations increase resistance to respiratory infections. With a deficiency of this microelement, a quantitative deficiency of antibody-producing cells and defects in the synthesis of the IgG 2 and IgA subclass are determined. A separate form of primary immunological deficiency has been described - “enteropathic acrodermatitis with combined immunological deficiency”, which is almost entirely corrected by taking zinc preparations, for example, zinc sulfate. The drug is taken continuously. Zinc oxide is prescribed in powder after meals with milk and juices. For acrodermatitis - 200-400 mg per day, then - 50 mg/day. For children, for infants 10-15 mg/day, for adolescents and adults - 15-20 mg/day. Prophylactically - 0.15 mg/kg/day.

Lithium has an immunotropic effect. Lithium chloride at a dose of 100 mg/kg or lithium carbonate at an age-related dose per dose causes an immunomodulatory effect in immunological deficiency caused by a deficiency of this microelement. Lithium enhances granulocytopoiesis, the production of colony-stimulating factor by bone marrow cells, which is used in the treatment of hypoplastic hematopoiesis, neutropenia and lymphopenia. Activates phagocytosis. Directions for using the drug: the dose is gradually increased from 100 mg to 800 mg/day, and then reduced to the original dose.

Phytoimmunomodulators Infusions and herbal decoctions have immunomodulatory (immunostimulating) activity.

Eleuthorococcus with normal immune status does not change immunity indicators. Has interferonogenic activity. When there is a deficiency in the number of T cells, it normalizes indicators, enhances the functional activity of T cells, activates phagocytosis, and nonspecific immune reactions. Apply 2 ml of alcohol extract 30 minutes before meals 3 times a day for 3-4 weeks. In children, to prevent relapses of acute respiratory infections, 1 drop/1 year of life, 1-3 times a day for 3-4 weeks.

Ginseng Increases performance and overall body resistance to diseases and adverse effects, does not cause harmful side effects and can be used for a long time. Ginseng root is a strong central nervous system stimulant, has no negative effects, and does not disturb sleep. Ginseng preparations stimulate tissue respiration, increase gas exchange, improve blood composition, normalize heart rhythm, increase light sensitivity of the eyes, accelerate healing processes, suppress the activity of certain bacteria, and increase resistance to radiation. It is recommended to use preparations from it in the autumn-winter period. The most stimulating effect is observed when using ginseng powder and tincture with 40 degrees alcohol. A single dosage is 15-25 drops of alcohol tincture (1:10) or 0.15-0.3 g of ginseng powder. Take 2-3 times a day before meals in courses of 30-40 days, then take a break.

Infusion of chamomile inflorescences Contains essential oils, azulene, antithymic acid, heteropolysaccharides with immunostimulating properties. Chamomile infusion is used to increase the activity of the immune system after hypothermia, during prolonged stressful situations, and in the autumn-spring period for the prevention of colds. The infusion is taken orally 30-50 ml 3 times a day for 5-15 days.

Echinacea ( Echinacea purpurea ) has an immunostimulating, anti-inflammatory effect, activates macrophages, secretion of cytokines, interferons, stimulates T cells. Used for the prevention of colds in the autumn-spring period, as well as for the treatment of viral and bacterial infections of the upper respiratory tract, genitourinary tract, etc. 40 drops 3 times a day, diluted with water, are recommended. Maintenance doses - 20 drops 3 times a day orally for 8 weeks.

Immunal - infusion of 80% Echinacea purpurea juice, 20% ethanol. Prescribe 20 drops orally every 2-3 hours for acute respiratory infections, flu, then 3 times a day. Course 1-8 weeks.

Biostimulants - adaptogens: tincture of lemongrass, decoctions and infusions of string, celandine, calendula, tricolor violet, licorice root and dandelion have an immunocorrective effect. There are drugs: glyceram, liquiriton, chest elixir, caleflon, calendula tincture.

Bacterioimmunotherapy Dysbiosis of the mucous membranes plays an important role in pathology. Antibiotic therapy, cytostatic and radiation therapy cause disruption of the biocenosis of the mucous membranes, primarily the intestines, and then dysbiosis occurs. Probiotic lactobacilli and bifidobacteria, colibacteria, releasing colicins, inhibit the growth of pathogenic bacteria. However, it is important not only to suppress pathogenic bacteria and fungi, but also that with dysbiosis, there is a deficiency of the necessary biologically active substances produced by the normal flora: vitamins (B 12, folic acid), E. coli lipopolysaccharides, which stimulate the activity of the immune system, etc. As a result, dysbiosis is accompanied by immunodeficiency. Therefore, preparations of natural flora are used to restore normal intestinal biocenosis, which plays an important role in stimulating the functions of the immune system.

Gram-positive lactobacilli and bifidobacteria stimulate anti-infectious and antitumor immunity and induce tolerance in allergic reactions. They directly induce a moderate release of cytokines by immunocompetent cells. As a result, the synthesis of secretory IgA is enhanced. On the other hand, lactobacilli, penetrating through the mucous membrane, can cause infection and induce a systemic immune response, therefore probiotic bacteria serve as strong immunomodulators, especially in immunodeficient organisms. Preparations of live bacteria are not used simultaneously with antibiotics and chemotherapy drugs that inhibit their growth.

Lactobacilli are antagonists of pathogenic microbes and secrete enzymes and vitamins. It is recommended to be prescribed together with specific bacteriophages that suppress pathogenic flora. It is not advisable to use them for candidiasis, since their acids enhance the growth of fungi.

Bifidumbacterin dry - dried live bifidobacteria. Adults: 5 tablets 2-3 times a day 20 minutes before meals. Course up to 1 month. For children - in bottles, diluted with warm boiled water (1 tablet: 1 teaspoon) 1-2 doses 2 times a day.

Used for dysbiosis, enteropathies, artificial feeding of children, treatment of premature babies, acute intestinal infections (dysentery, salmonellosis, etc.), chronic intestinal diseases (gastritis, duodenitis, colitis), radiation and chemotherapy of tumors, candidal vaginitis, food intolerance and food allergies, dermatitis, eczema, normalization of the microflora of the oral mucosa in case of stomatitis, periodontitis, diabetes, chronic diseases of the liver and pancreas, work in harmful and extreme conditions.

Bificol dry - live dried bifidobacteria and E. coli vrt7. Adults and children over 3 years old - 20-30 minutes before meals, 3-5 tablets 2 times a day, washed down with water. Course 2-6 weeks.

Bifiform contains at least 10 7 Bifidobacterium lobgum, and also 10 7 Ep-fgrococcus faecium in capsules. For dysbacteriosis of I-II degree, 1 capsule 3 times a day, course 10 days, for dysbiosis of II-III degree, increase the course to 2-2.5 weeks -

Linux - a combined preparation, contains three components of natural microflora from different parts of the intestine: in one capsule - 1.2x10 7 live lyophilized bacteria Bifidobacterium infantis, Lactobacillus, Cl. dophilus And Str. faecium resistant to antibiotics and chemotherapy. They support microbiocenosis in all parts of the intestine - from the small intestine to the rectum. Prescribed: for adults, 2 capsules 3 times a day with boiled water or milk; children under 2 years old - 1 capsule 3 times a day, with liquid or mixing the contents of the capsule with it.

Colibacterin dry - dried live E. coli, strain M-l7, which is an antagonist for pathogenic microbes, stimulates the immune system, as well as enzymes and vitamins.. Adults 3-5 tablets 2 times a day, 30-40 minutes before meals, washed down with alkaline mineral water. Course 3 weeks -1.5 months.

Bificol - combination drug.

Bactisubtil - sporobacteria culture GR-5832 (ATCC 14893) 35 mg-10 9 spores, used for diarrhea, dysbiosis, 1 drop 3-10 times a day 1 hour before meals.

Enterol-250 , unlike bacteria-containing drugs, contains saccharomycetes yeast (Saccharomycetes boulardii), which serve as antagonists of pathogenic bacteria and fungi. Recommended for diarrhea, dysbacteriosis, and can be used in combination with antibacterial therapy. Children under 3 years of age are prescribed 1 capsule 1-2 times a day for 5 days, children over 3 years of age and adults 1 capsule 2 times a day for 7-10 days.

Hilak forte contains products of metabolic activity of probiotic strains of lactobacilli and normal intestinal microorganisms - Escherichia coli and fecal streptococcus: lactic acid, amino acids, short-chain fatty acids, lactose. Compatible with taking antibiotics. The simultaneous use of antacid drugs is not recommended due to the possible neutralization of lactic acid, which is part of Hilak-Forte. Prescribed in a dose of 20-40 drops 3 times a day for 2-3 weeks (infants 15-30 drops 3 times a day), taken in a small amount of liquid before or during meals, excluding milk and dairy products.

Gastrofarm - living lyophilized cells Lactobacillus bulgaricus 51 and metabolites of their vital activity (lactic and malic acids, nucleic acids, a number of amino acids, polypeptides, polysaccharides). Inside, 3 times a day, chewing with a small amount of water. A single dose for children is S tablets, for adults - 1-2 tablets.

Immunomodulatory effects of antibiotics Opportunistic microbes (staphylococci, streptococci, Escherichia coli, etc.) are etiological factors and also causative agents of most diseases of an infectious-inflammatory nature. Therefore, the main therapeutic measure is antibacterial therapy, in particular the use of antibiotics. Attempts to “sterilize” a patient with antibacterial agents lead to dysbacteriosis and mycoses, which create new problems.

Opportunistic microbes do not cause disease in most people and are normal inhabitants of the skin and mucous membranes. The reason for their activation is insufficient resistance of the body - immunodeficiency. Therefore, the basis of infectious and inflammatory diseases are congenital or acquired, acute and chronic immunodeficiencies, which create favorable conditions for the proliferation of microbes that are normally constantly eliminated by immune factors. An example of a common acute immunodeficiency is the cold syndrome, when, against the background of hypothermia, the body’s natural resistance to opportunistic microbes is inhibited.

From the above it follows that without restoring the body’s reactivity, suppression of microflora alone is often insufficient for complete recovery. Moreover, many antibacterial agents suppress the immune system and create conditions for contamination of the body with antibiotic-resistant strains. The problem is further aggravated by the widespread “prophylactic” use of antibacterial agents for viral infections. The main ways to solve the problem: simultaneous use of antibiotics and agents that normalize the suppressed parts of the immune system; additional use of immunorehabilitation agents; maximum preservation and restoration of the body’s endoecology. There are two possible effects of antibiotics on the immune response: those associated with lysis or damage to bacteria and those associated with a direct effect on the cells of the immune system.

1. Effects mediated by damaged bacteria:

- inhibition of cell wall synthesis (penicillins, clindacimine, cephalosporins, carbapenems, etc.) - reduces the resistance of bacterial cells to the action of bactericidal factors of leukocytes and macrophages;

inhibition of protein synthesis (macrolides, rifampicin, tetracyclines, fluoroquinolones, etc.) causes changes in the cell membrane of microorganisms and can enhance phagocytosis by reducing the expression on the surface of bacterial cells of proteins with antiphagocytic functions, at the same time, these antibiotics suppress the immune response due to disruption protein synthesis in cells of the immune system;

disintegration of the membrane of gram-negative bacteria and increasing its permeability (aminoglycosides, polymyxin B) increases the sensitivity of microorganisms to the action of bactericidal factors.

2. The effects of antibiotics due to the release of biologically active substances from microorganisms during their destruction: endotoxins, exotoxins, glycopeptides, etc. Small doses of endotoxins are necessary for the normal development of immunity, have a beneficial effect, stimulate nonspecific resistance to bacterial and viral infections, as well as cancer. This can be seen in the example of E. coli, which is a normal inhabitant of the intestines. When it is destroyed, a small amount of endotoxin is released, stimulating local and general immunity. Therefore, for such prolonged infections, preparations of bacterial lipopolysaccharides - prodigiosan, pyrogenal and lycopid - are often effective. However, with severe infection and the release of large amounts of endotoxin into the bloodstream, the cytokines induced by it (IL-1, TNF-α) can cause inhibition of phagocytosis, severe toxicosis, up to toxic-septic shock with a drop in cardiovascular activity. On the other hand, intensive lysis of a large number of bacteria and the release of endotoxins can lead to adverse reactions such as Jarish-Herxheimer.

Effects caused by the direct influence of antibiotics on the immune system:

Beta-lactam antibiotics enhance phagocytosis and chemotaxis of leukocytes, but in large doses they can inhibit antibody formation and bactericidal blood;

Cephalosporins, by binding to neutrophils, increase their bactericidal activity, chemotaxis and oxidative metabolism in patients with immunodeficiencies.

Gentamicin reduces phagocytosis and chemotaxis of granulocytes and RBTL.

Macrolides (erythromycin, roxithromycin and azithromycin) stimulate phagocyte functions, bactericidal activity, chemotaxis, and cytokine synthesis (IL-1, etc.).

Fluoroquinolones enhance the proliferation of cells of the immune system, increase the synthesis of IL-2, phagocytosis and bactericidal activity.

Tetracycline, doxycycline inhibit phagocytes and antibody synthesis.

The immunomodulatory effects of antibiotics on the immune system lead to the development of allergic reactions. The basis is the interaction of antibiotics as haptens with cells of the immune system and the activation of a specific immune response.

Immunomodulators are a group of pharmacological drugs that activate the body’s immunological defense at the cellular or humoral level. These drugs stimulate the immune system and increase the body's nonspecific resistance.

main organs of the human immune system

Immunity is a unique system of the human body that is capable of destroying foreign substances and needs proper correction. Normally, immunocompetent cells are produced in response to the introduction of pathogenic biological agents into the body - viruses, microbes and other infectious agents. Immunodeficiency states are characterized by decreased production of these cells and are characterized by frequent morbidity. Immunomodulators are special drugs, united by a common name and a similar mechanism of action, used to prevent various ailments and strengthen the immune system.

Currently, the pharmacological industry produces a huge number of products that have immunostimulating, immunomodulating, immunocorrective and immunosuppressive effects. They are freely sold in pharmacy chains. Most of them have side effects and have a negative impact on the body. Before purchasing such medications, you should consult your doctor.

Immunostimulants strengthen the human immune system, ensure more efficient functioning of the immune system and provoke the production of protective cellular components. Immunostimulants are harmless for persons who do not have immune system disorders and exacerbations of chronic pathologies.
Immunomodulators correct the balance of immunocompetent cells in autoimmune diseases and balance all components of the immune system, suppressing or increasing their activity.
Immunocorrectors have an effect only on certain structures of the immune system, normalizing their activity.
Immunosuppressants suppress the production of immune components in cases where its hyperactivity causes harm to the human body.

Self-medication and inadequate medication use can lead to the development of autoimmune pathology, in which the body begins to perceive its own cells as foreign and fights them. Immunostimulants should be taken according to strict indications and as prescribed by the attending physician. This is especially true for children, because their immune system is fully formed only by the age of 14.

But in some cases, you simply cannot do without taking drugs from this group. In severe diseases with a high risk of developing serious complications, taking immunostimulants is justified even in children and pregnant women. Most immunomodulators are low-toxic and quite effective.

Use of immunostimulants

Preliminary immunocorrection is aimed at eliminating the underlying pathology without the use of basic therapy drugs. It is prescribed to persons with diseases of the kidneys, digestive system, rheumatism, and in preparation for surgical interventions.

Diseases for which immunostimulants are used:

Congenital immunodeficiency,
Malignant neoplasms,
Inflammation of viral and bacterial etiology,
Mycoses and protozooses,
Helminthiasis,
Kidney and liver pathology,
Endocrinopathology – diabetes mellitus and other metabolic disorders,
Immunosuppression due to the use of certain medications - cytostatics, glucocorticosteroids, NSAIDs, antibiotics, antidepressants, anticoagulants,
Immunodeficiency caused by ionizing radiation, excessive alcohol intake, severe stress,
Allergy,
Conditions after transplantation,
Secondary post-traumatic and post-intoxication immunodeficiency states.

The presence of signs of immune deficiency is an absolute indication for the use of immunostimulants in children. Only a pediatrician can choose the best immunomodulator for children.

People who are most often prescribed immunomodulators:

Children with weak immune systems
Elderly people with weakened immune systems,
People with a busy lifestyle.

Treatment with immunomodulators should be under the supervision of a physician and an immunological blood test.

Classification

The list of modern immunomodulators today is very large. Depending on their origin, immunostimulants are distinguished:

Independent use of immunostimulants is rarely justified. They are usually used as an adjunct to the main treatment of pathology. The choice of drug is determined by the characteristics of immunological disorders in the patient’s body. The effectiveness of drugs is considered to be maximum during exacerbation of the pathology. The duration of therapy usually varies from 1 to 9 months. The use of adequate doses of medication and proper adherence to the treatment regimen allows immunostimulants to fully realize their therapeutic effects.

Some probiotics, cytostatics, hormones, vitamins, antibacterial drugs, and immunoglobulins also have an immunomodulatory effect.

Synthetic immunostimulants

Synthetic adaptogens have an immunostimulating effect on the body and increase its resistance to adverse factors. The main representatives of this group are “Dibazol” and “Bemitil”. Due to their pronounced immunostimulating activity, the drugs have an antiasthenic effect and help the body quickly recover after prolonged exposure to extreme conditions.

For frequent and prolonged infections, Dibazol is combined with Levamisole or Decamevit for preventive and therapeutic purposes.

Endogenous immunostimulants

This group includes preparations of the thymus, red bone marrow and placenta.

Thymic peptides are produced by thymus cells and regulate the functioning of the immune system. They change the functions of T-lymphocytes and restore the balance of their subpopulations. After the use of endogenous immunostimulants, the number of cells in the blood is normalized, which indicates their pronounced immunomodulatory effect. Endogenous immunostimulants enhance the production of interferons and increase the activity of immunocompetent cells.

"Timalin" has an immunomodulatory effect, activates regeneration and repair processes. It stimulates cellular immunity and phagocytosis, normalizes the number of lymphocytes, increases the secretion of interferons, and restores immunological reactivity. This drug is used to treat immunodeficiency conditions that have developed against the background of acute and chronic infections and destructive processes.
"Imunofan"– a drug widely used in cases where the human immune system cannot independently resist the disease and requires pharmacological support. It stimulates the immune system, removes toxins and free radicals from the body, and has a hepatoprotective effect.

Interferons

Interferons increase the nonspecific resistance of the human body and protect it from viral, bacterial or other antigenic attacks. The most effective drugs that have a similar effect are "Cycloferon", "Viferon", "Anaferon", "Arbidol". They contain synthesized proteins that push the body to produce its own interferons.

Naturally occurring drugs include leukocyte human interferon.

Long-term use of drugs in this group minimizes their effectiveness and suppresses a person’s own immunity, which ceases to function actively. Inadequate and too long-term use of them has a negative impact on the immunity of adults and children.

In combination with other medications, interferons are prescribed to patients with viral infections, laryngeal papillomatosis, and cancer. They are used intranasally, orally, intramuscularly and intravenously.

Preparations of microbial origin

Medicines in this group have a direct effect on the monocyte-macrophage system. Activated blood cells begin to produce cytokines, which trigger innate and acquired immune responses. The main task of these drugs is to remove pathogenic microbes from the body.

Plant adaptogens

Herbal adaptogens include extracts of echinacea, eleutherococcus, ginseng, and lemongrass. These are “mild” immunostimulants, widely used in clinical practice. Drugs from this group are prescribed to patients with immunodeficiency without a preliminary immunological examination. Adaptogens trigger the work of enzyme systems and biosynthetic processes, and activate the body’s nonspecific resistance.

The use of plant adaptogens for prophylactic purposes reduces the incidence of acute respiratory viral infections and, resists the development of radiation sickness, weakens the toxic effect of cytostatics.

To prevent a number of diseases, as well as for a speedy recovery, patients are recommended to drink ginger tea or cinnamon tea daily, and take black peppercorns.

Video: about immunity – School of Dr. Komarovsky

Orenburg State Agrarian University

Department of Microbiology

Abstract on the topic:

"Microbial immunomodulators"

Orenburg, 2010

1. Immunity and immune system.

2. Immunomodulators

1. Immunity and immune system.

Immunity is the protection of the body from genetically foreign agents of exogenous and endogenous origin, aimed at preserving and maintaining the genetic homeostasis of the body, its structural, functional, biochemical integrity and antigenic individuality. Immunity is one of the most important characteristics for all living organisms created in the process of evolution. The principle of operation of defense mechanisms is to recognize, process and eliminate foreign structures. Protection is carried out using two systems - nonspecific (innate, natural) and specific (acquired) immunity. These two systems represent two stages of a single process of protecting the body. Nonspecific immunity acts as the first line of defense and as its final stage, and the acquired immunity system performs intermediate functions of specific recognition and memory of a foreign agent and the activation of powerful innate immunity at the final stage of the process. The innate immune system operates on the basis of inflammation and phagocytosis, as well as protective proteins (complement, interferons, fibronectin, etc.). This system reacts only to corpuscular agents (microorganisms, foreign cells, etc.) and toxic substances that destroy cells and tissues, or rather , on the corpuscular products of this destruction. The second and most complex system - acquired immunity - is based on the specific functions of lymphocytes, blood cells that recognize foreign macromolecules and react to them either directly or by producing protective protein molecules (antibodies).

In addition to somatic and infectious diseases, which are widespread among people, the human body is affected by social (inadequate and irrational nutrition, living conditions, occupational hazards), environmental factors, and medical measures (surgical interventions, stress, etc.) that are unfavorable to health. First of all, the immune system suffers, and secondary immunodeficiencies occur. Despite the constant improvement of methods and tactics of basic disease therapy and the use of deep reserve drugs using non-drug methods of influence, the effectiveness of treatment remains at a fairly low level. Often the reason for these features in the development, course and outcome of diseases is the presence of certain disorders of the immune system in patients. Research conducted in recent years in many countries around the world has made it possible to develop and introduce into widespread clinical practice new integrated approaches to the treatment and prevention of various nosological forms of diseases using immunotropic drugs of targeted action, taking into account the level and degree of disorders in the immune system. An important aspect in preventing relapses and treating diseases, as well as in preventing immunodeficiencies, is the combination of basic therapy with rational immunocorrection. Currently, one of the urgent tasks of immunopharmacology is the development of new drugs that combine such important characteristics as effectiveness and safety of use.

2. Immunomodulators

Immunomodulators– these are drugs that, when used in therapeutic doses, restore the functions of the immune system (effective immune defense).

Immunomodulators (immunocorrectors) - a group of drugs of biological (preparations from animal organs, plant materials), microbiological and synthetic origin, which have the ability to normalize immune reactions.

2.1. Clinical use of immunomodulators.

The most justified use of immunomodulators seems to be in cases of immunodeficiency, manifested by an increased infectious morbidity. The main target of immunomodulatory drugs remains secondary immunodeficiencies, which are manifested by frequent recurrent, difficult-to-treat infectious and inflammatory diseases of all locations and any etiology. Each chronic infectious-inflammatory process is based on changes in the immune system, which are one of the reasons for the persistence of this process. Studying the parameters of the immune system may not always reveal these changes. Therefore, in the presence of a chronic infectious-inflammatory process, immunomodulatory drugs can be prescribed even if an immunodiagnostic study does not reveal significant deviations in the immune status.

As a rule, in such processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungals, antivirals or other chemotherapeutic drugs. According to experts, in all cases when antimicrobial agents are used for phenomena of secondary immunological deficiency, it is advisable to prescribe immunomodulatory drugs.

The main requirements for immunotropic drugs are:

Immunomodulatory properties;
high efficiency;
natural origin;
safety, harmlessness;
no contraindications;
lack of addiction;
no side effects;
absence of carcinogenic effects;
lack of induction of immunopathological reactions;
do not cause excessive sensitization and do not potentiate it in other medications;
easily metabolized and excreted from the body;
do not interact with other drugs and
have high compatibility with them;
non-parenteral routes of administration.

Currently, the basic principles of immunotherapy have been developed and approved:

1. Mandatory determination of immune status before starting immunotherapy;
2. Determination of the level and extent of damage to the immune system;
3. Monitoring the dynamics of immune status during immunotherapy;
4. Use of immunomodulators only in the presence of characteristic clinical signs and changes in immune status indicators
5. Prescription of immunomodulators for preventive purposes to maintain immune status (oncology, surgical interventions, stress, environmental, occupational and other influences)

Currently, there are 6 main groups of immunomodulators based on their origin:

Microbial immunomodulators;

Thymic immunomodulators;
bone marrow immunomodulators;
cytokines;
nucleic acids;
chemically pure.

3. Immunomodulators of microbial origin

Immunomodulators of microbial origin can be divided into three generations. The first drug approved for medical use as an immunostimulant was the BCG vaccine, which has a pronounced ability to enhance factors of both innate and acquired immunity.

First-generation microbial preparations also include drugs such as pyrogenal and prodigiosan, which are polysaccharides of bacterial origin.

Currently, due to pyrogenicity and other side effects, they are rarely used.

Second-generation microbial preparations include lysates (Bronchomunal, IPC-19, Imudon, the Swiss-made drug Broncho-Vaxom, which recently appeared on the Russian pharmaceutical market) and ribosomes (Ribomunil) of bacteria, which are mainly related to the causative agents of respiratory infections Klebsiella pneumoniae, Streptococcus pneumoniae , Streptococcus pyogenes, Haemophilus influezae, etc. These drugs have a dual purpose: specific (vaccinating) and nonspecific (immunostimulating).

Likopid, which can be classified as a third-generation microbial preparation, consists of a natural disaccharide - glucosaminylmuramyl and a synthetic dipeptide - L-alanyl-D-isoglutamine attached to it. In the body, the main target for immunomodulators of microbial origin are phagocytic cells. Under the influence of these drugs, the functional properties of phagocytes are enhanced (phagocytosis and intracellular killing of absorbed bacteria are increased), and the production of anti-inflammatory cytokines necessary for the initiation of humoral and cellular immunity increases. As a result, antibody production may increase and the formation of antigen-specific T-helper and T-killer cells may be activated.

3.1. Preparations of microbial origin.

Bifiform, bifidumbacterin, probifor, linex, acipol, kipacid, enterol, bactisubtil, bificol, gastrofarm, acylact, bronchomunal, BCG, imudon, IRS-19, sodium nucleinate, prodigiosan, ribomunil, ruzam

Table 4.The main immunomodulators of microbial origin, approved for use in Russia

A drug	Origin	Clinical indications
Broncho-munal	Bacteria lysate Str. pneumonia, H. influenzae, Klebsiella pneumonia, Kl. ozaenae, Staphylococcus aureus, Str. viridans, Str. pyogenes, M. catarrhalis	Treatment and prevention of recurrent respiratory tract infections
	Bacteria lysate L.lactis, L. acidophilus, L. helveticus, L. fermentatum,St. aureus, Kl. pneumonia, Corynobacterium pseudodiphteriticum, Fusobacterium nucleatum, Candida albicans	Gingivitis, periodontitis, alveolar pyorrhea, pericoronitis, periodontal abscesses, glossitis, stomatitis, oral candidiasis
	Lysate Str. pneumonia,St. aureus, Neisseria,Kl. pneumonia, M. cataralis, H. influenzae,Acinetobacter, Enterococcus faecium, E. faecalis	Therapy and prevention of recurrent upper respiratory tract infections
Sodium nucleinate	Sodium salt of nucleic acid derived from yeast	Chronic viral and bacterial infections, leukopenia
Pyrognal	Lipopolysaccharide Ps. aerogenosa	Chronic infections, some allergic processes, psoriasis, dermatoses
Prodigiosan	Lipopolysaccharide Ps. prodigisiosum	Chronic infections, long-term non-healing wounds
Ribomunil	Ribosomes Kl. pneumonia, Str. pneumonia,Str. pyogenes, H. influenzae, peptidoglycan Kl. pneumonia	Chronic nonspecific respiratory diseases
	Waste product of thermophilic staphylococcus	Chronic nonspecific lung diseases, bronchial asthma

The immunomodulatory role of Mycobacterium tuberculosis has been known for more than half a century. The BCG vaccine currently has no independent significance as an immunomodulator. An exception is the method of immunotherapy for bladder cancer using the BCG-Imuron vaccine. The BCG-Imuron vaccine is live lyophilized bacteria of the BCG-1 vaccine strain. The drug is used in the form of instillations into the bladder.

Living mycobacteria, multiplying intracellularly, lead to nonspecific stimulation of the cellular immune response. BCG-Imuron is intended for the prevention of relapses of superficial bladder cancer after surgical removal of the tumor, as well as for the treatment of small bladder tumors that cannot be removed.

Study of the mechanism of the immunomodulatory effect of the BCG vaccine. showed that it is reproduced using the inner layer of the cell wall of Mycobacterium tuberculosis - peptidoglycan, and the active principle in peptidoglycan is muramyl dipeptide, which is part of the peptidoglycan of the cell wall of almost all known gram-positive and gram-negative bacteria. However, due to high pyrogenicity and other undesirable side effects, muramyl dipeptide itself turned out to be unsuitable for clinical use. Therefore, the search for its structural analogues began.

This is how the drug Lykopid (glucosaminylmuramyl dipeptide) appeared, which, along with low pyrogenicity, has higher immunomodulatory potential.

Lykopid has an immunomodulatory effect primarily due to the activation of cells of the phagocytic immune system (neutrophils and macrophages). The latter, by phagocytosis, destroy pathogenic microorganisms and, at the same time, secrete mediators of natural immunity - cytokines (interleukin-1, tumor necrosis factor, colony stimulating factor, gamma interferon), which, affecting a wide range of target cells, cause further development protective reaction of the body. Ultimately, Lykopid affects all three main components of immunity: phagocytosis, cellular and humoral immunity, stimulates leukopoiesis and regenerative processes.

The main indications for prescribing licopid: chronic nonspecific lung diseases, both in the acute stage and in remission; acute and chronic purulent-inflammatory processes (postoperative, post-traumatic, wound), trophic ulcers; tuberculosis; acute and chronic viral infections, especially genital and labial herpes, herpetic keratitis and keratouveitis, herpes zoster, cytomegalovirus infection; lesions of the cervix caused by the human papillomavirus; bacterial and candidal vaginitis; urogenital infections.

The advantage of licopid is its ability to be used in pediatrics, including neonatology. Lykopid is used in the treatment of bacterial pneumonia in full-term and premature infants. Likopid is used in the complex treatment of chronic viral hepatitis in children. Since Likopid is able to stimulate the maturation of glucuronyltransferase in the liver of newborns, its effectiveness in conjugative hyperbilirubinemia in the neonatal period is being tested.

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