Dysfunction of the immune system in acute alcohol intoxication and alcoholism ulyanova, lyudmila ivanovna.

Among the most common causes of morbidity and mortality in patients with alcoholism and drug addiction are severe infections, which, in turn, are the result of impaired immune function.

The weakening of the immune system also leads to an increase in the incidence of tumors in this contingent, the development of autoimmune diseases, and disruption of tissue regeneration. The study of the state of immunity in narcological patients is of great importance for the inclusion of immunocorrectors in therapeutic programs and can contribute to specific immunodiagnostics. Alcohol abuse, alcoholism and immune system dysfunction

Malicious action overuse alcohol on human health has been described for a long time, including, first of all, damage to the liver and high performance morbidity and mortality from infectious diseases - such as pneumonia, etc. Numerous clinical and experimental studies have made it possible to establish the cause of the increased frequency of infectious diseases in people who abuse alcohol - this is immunodeficiency. There is also good reason to believe that alcoholic organ damage, such as alcoholic liver disease, is partly due to or exacerbated by the development of autoimmune processes triggered by alcohol abuse.

Diseases caused by the occurrence of immunodeficiency. As early as the beginning of the 20th century, it was noticed that alcoholics die of pneumonia more than twice as often as the rest of the population. The high incidence of pneumonia, and its severe forms, persists today, despite the use of antibiotics, and people who abuse alcohol are still more susceptible to the disease. bacterial pneumonia than nondrinkers. This conclusion is confirmed by a large number clinical research(see review by V.T. Sook, 1998). It has also been shown that a high percentage of patients with pneumonia abuse alcohol. Alcohol abusers are also more susceptible to a number of other infections, including septicemia. In some cases, generalization of infection occurs due to the ability of pneumonia pathogens to penetrate into the bloodstream. Generalization of infection in alcoholics is also facilitated by the presence in the body of other sources of infection (diseases of the genitourinary tract, bacterial peritonitis, biliary tract infections).

In patients with alcoholism, the incidence of tuberculosis is increased, which is 16%, but can rise to 35% or more (according to the US Center for Disease Control - R.T. Sook, 1998). When observing contingents of people who abuse drugs and alcohol for many years, it was found that tuberculosis occurs in them 15-200 times more often than in control populations. In recent years, increased morbidity and mortality from tuberculosis in these contingents persist, which is big problem for society, especially in connection with the emergence of drug-resistant strains of the causative agent of this disease.

Whether alcohol consumption increases susceptibility to HIV infection at the time of infection, and whether alcohol consumption by infected individuals increases their risk of progressing from asymptomatic infection to AIDS and profound immunodeficiency, there is currently no clear answer. One group of researchers reported accelerated HIV replication after cell donors consumed alcohol. Other experts have not found a significant effect of a single dose of alcohol on HIV replication (NT Sook, 1998). In a 5-year study of a group of HIV-infected patients who used drugs intravenously, it was found that damage to T-cell subpopulations was more pronounced among heavy drinkers than among nondrinkers or light drinkers.

The advent of tests for antibodies to hepatitis B (HB\/) and C (HCV) viruses has contributed to interest in elucidating the possible role of these viruses in causing alcoholic cirrhosis. According to modern studies, in which the influence of risk factors for infection with HB\/ and NSS not associated with alcohol consumption was excluded, among “pure” alcoholics there is no increase in the incidence of HBV; however, HC\/ is detected in them approximately 10% more often. An important fact is the detection of HB \/ or HC \/ viruses in people who abuse alcohol in 10-50% of cases, according to various researchers (RT Sook, 1998). These patients simultaneously suffer from two diseases (alcoholism and viral hepatitis), which may have an additive or synergistic effect on the development of liver damage. In addition, both of these conditions affect immune system with the development of immunodeficiency or autoimmune disorders. In patients with alcoholism, the frequency of occurrence of some other infections is also increased (lung abscess, empyema, spontaneous bacterial peritonitis, diphtheria, meningitis, etc.).

Diseases with an autoimmune component. A serious complication of chronic alcohol intoxication(CHAI) is the development of alcoholic liver damage with subsequent liver failure. In alcoholic hepatitis, liver function tests indicate necrosis of liver cells and the presence of an acute inflammatory process. Histological examination liver reveals, in addition to the death of liver cells, infiltration of cells of the immune system, sometimes very significant. The role of this system in liver damage in such patients is evidenced by two clinical facts. First, the condition of patients with alcoholic hepatitis often continues to worsen within one to several weeks after the cessation of alcohol intake, indicating that the pathological process during this period is not associated with the effects of alcohol. Secondly, if alcoholics who have recovered from alcoholic hepatitis start drinking again, they tend to have new exacerbations of hepatitis, and these exacerbations are more severe and develop with the use of smaller amounts of alcohol than before. These observations suggest an autoimmune process in which an immune reaction occurs to some substrate of one's own liver. Repeated alcohol use intensifies this reaction.

humoral immunity. Patients with alcoholism are characterized by a significant increase in the level of immunoglobulins in the blood serum (V.T. Sook, 1998). Immunoglobulins of all major classes can be increased: A (1dA), C (1dS) and M (1dM). As a rule, 1gA is elevated both in alcoholic patients without liver damage and in patients with alcoholic liver damage, while the 1gA level is elevated only in patients with alcoholic hepatitis. In turn, 1dM increases only in patients with active alcoholic hepatitis. In addition, in patients with alcoholism, deposits of 1gA are often found in tissues, especially in the skin, liver and kidneys. It is generally accepted that an increase in the level of antibodies of one or another class of immunoglobulins is associated with the development of specific immunity (as, for example, with successful vaccination). However, in patients with alcoholism, a significant increase in the level of immunoglobulins is often combined with immunodeficiency. It is believed that the marked increase is a consequence of impaired regulation of antibody production and/or a reflection of autoimmune processes. This assumption was supported by the discovery of autoantibodies to a large number tissues and molecules. It has been shown, for example, that CAI is accompanied by increased production of antibodies to brain and liver antigens (N.B. Gamaleya, 1990), to serum antigens, in particular, albumin (Gamaleya et al., 1997) and neurotransmitters (L.A. Basharova , 1992; S.I. Tronnikov, 1994), food antigens (K.D. Plecyty, T.V. Davydova, 1989). A consequence of an increase in the level of autoantibodies may be an increase in the level of circulating immune complexes- CEC (Gamaleya, 1990).

In patients with alcoholism, it was also noted important fact- an increase in the level of antibodies to proteins altered by the reactogenic product of ethanol metabolism in the body - acetaldehyde. In particular, antibodies to acetaldehyde-modified hemoglobin (Z.L/Orga11 et al., 1990) and modified albumin have been found (Gamaleya et al., 2000). The level of class A antibodies to acetaldehyde-modified human serum albumin was taken as the basis for the development of immunodiagnostics of chronic alcohol intoxication (Gamaleya et al. 1999).

The role of acetaldehyde adducts and antibodies to them in the pathogenesis of alcoholic damage to the liver and other organs. By now, quite a lot of evidence has already accumulated in favor of the involvement of immune mechanisms in the pathogenesis of alcoholic liver damage. In the organism, ethanol is metabolized with the participation of alcohol dehydrohegase and cytochrome P450 with the formation of acetaldehyde. 1p Mo acetal-1egide forms stable |\|-ethyl-lysine conjugates (adducts) with various proteins of the body, including intracellular proteins: hemoglobin, cytochromes P4502E1 and P4503A, and circulating protein with a molecular weight of 37 KD. Following the use of ethanol, specific antibodies appear in the blood serum, the titr of which correlates with the severity of liver damage. Antibodies to the acetaldehyde adduct of cytochrome P4502E1 were found in more than 1/85% of patients with alcoholic liver cirrhosis (P.C101 et al., 1996).

With the help of antibodies to acetaldehyde adducts, the appearance of such adducts in the liver of experimental animals after the consumption of ethanol, as well as in the culture of rat hepatocytes treated with ethanol, was proved (N. Wakouata e (a1., 1993). Moreover, using various methods It was shown that as a result of long-term consumption of ethanol by animals, acetaldehyde adducts (AA) appear in the cytosol and microsomes of the liver, and adducts of acetaldehyde and the plasma membrane of the liver are also formed. Partly confirmed the role of AA in the pathogenesis of alcoholic hepatitis experiments on immunization of animals with such adducts (N. Ukouata et al., 1993). Guinea pigs were immunized with hemoglobin and acetaldehyde adducts and simultaneously fed ethanol for 40 days. As a result, the animals developed liver necrosis with infiltration of mononuclear cells in the liver lobules. In severe cases, the formation of lymphoid follicles was observed. The noted changes were accompanied by an increase in the activity of AST and LDH in the blood serum, as well as the titers of circulating antibodies to acetaldehyde adducts. In control experiments, when immunization with unmodified hemoglobin was performed, only fatty changes in the liver were observed, and in the case of immunization with adducts not accompanied by ethanol consumption, only minimal inflammatory changes were noted in the liver. Peripheral blood lymphocytes obtained from animals with developed hepatitis were stimulated by AA to a much greater extent than lymphocytes from control animals. According to the morphopathological picture, the experimental hepatitis obtained from immunized animals was more similar to autoimmune or viral hepatitis than to alcoholic hepatitis.

The conducted studies do not fully explain the pathogenesis of alcoholic liver damage in humans, however, they clearly show that under certain conditions immunological reaction against M can lead to liver damage. One of the possible mechanisms of liver damage by antibodies to AA proteins, in particular, serum albumin, may be the cross-reaction of such antibodies with the adduct of acetaldehyde and phosphatidylethanolamine, built into the phospholipid layer of the surface membrane of hepatocytes. Following this interaction, the antibody-antigen complex can recruit and activate macrophages, as well as attach complement, resulting in cell lysis. Another possible mechanism of hepatotoxicity may be associated with antibodies to collagen AA, which are found in the blood serum of patients with alcoholic and non-alcoholic hepatitis. The role of these antibodies in liver damage is evidenced by the correlation of their level with the severity of inflammation and the activity of AST and gamma-glutamyl transpeptidase.

In addition to liver proteins, AA can also be formed with cytosolic proteins of the heart muscle. In patients with alcoholic cardiomyopathy, antibodies to such adducts were found in 33% of cases, while in the control group (persons without heart disease or with heart disease of non-alcoholic origin), as well as in persons with alcoholic liver disease - only in 3% (A .A.Harcomte et al., 1995). The presence of such antibodies can be used in the diagnosis of heart lesions, as well as indicate their role in the pathogenesis of such lesions.

The results obtained in work with adducts and antibodies to them, as well as the discovery of the ability of such antibodies to exhibit cellular cytotoxicity, are a big step forward in understanding the mechanisms of autoimmune immune reactions and tissue damage from alcohol. They give possible explanation the fact of worsening of the manifestations of the clinic of alcoholic hepatitis during subsequent exacerbations and explain the progression of tissue damage to the liver for a certain period of time after the cessation of alcohol intake.

Cellular immunity. Another component of the immunological reactivity of the body is cell-mediated immunity, in which the effector function of the immune response is carried out by lymphocytes. The violation of cellular immunity in patients with alcoholism is evidenced by the close relationship that exists between alcoholism and the incidence of tuberculosis and some tumor diseases, in which, as is known, the function of T-lymphocytes changes first of all (Plecity, Davydova, 1989). T cells carry out an effector defense mechanism against microorganisms and tumors, and also interact with B lymphocytes that produce antibodies to complex protein antigens. The result of this interaction is the synthesis of T-dependent antibodies, mainly 1dC. The interaction of immunocompetent cells is carried out with the help of cytokines. it T cell factors growth (IL-2 and IL-4), factors that interact with B cells (IL-2, 4, 5,6 and 7), as well as cytokines that activate mononuclear phagocytes that kill tumor cells and intracellular microorganisms (interferons).

In patients with alcoholism, multiple disorders of cellular immunity have been described - such as a decrease in skin reactivity (delayed-type hypersensitivity - DTH) to tuberculin and fungal antigens, a decrease in the number of T-lymphocytes, mainly due to a subpopulation of T-helpers in normal level T-suppressors (which leads to a decrease in the TxDs index), and B-lymphocytes. Evaluation of the functional activity of isolated lymphocytes in the form of a proliferative reaction (blast transformation reaction) in response to stimulation of t yKgo with various mitogens revealed a significant decrease in this reaction in the case of lymphocytes from alcoholic patients compared with lymphocytes from individuals who do not abuse alcohol. Our studies also showed that in patients with alcoholism without severe liver damage in the state of alcohol withdrawal syndrome (AAS), there was a significant decrease in comparison with a group of healthy blood donors in both spontaneous (not stimulated) and mitogen-stimulated proliferation of peripheral blood lymphocytes 1p y11go (Gamaleya et al., 1994). It should be emphasized that the proliferative response of lymphocytes to mitogens is regarded as a model of the in vitro proliferative expansion of cells under the influence of antigens of mushno. The most persistent change observed within 24 days after admission of patients to the hospital in the state of AAS was a decrease in the functional activity of T-lymphocytes (helpers and suppressors). In patients with alcoholism, for the first time, we noted a change in the temporal parameters of the activity of T- and B-cells, indicating possible disturbances in the system of regulation of this activity, which, in turn, can lead to a change in the cooperative interaction of cells during the immune response (Gamaleya et al. , 2000). In patients with alcoholism in remission, who underwent inpatient anti-alcohol treatment and did not drink alcohol for 60 days, there was a restoration of the proliferative activity of B-lymphocytes, while the activity of T-lymphocytes (both helpers and suppressors) remained at a low level.

In patients with alcoholism without liver damage, as a rule, the normal content of lymphocytes in the peripheral blood is detected, while patients with simultaneous liver damage are characterized by various abnormalities, depending on the stage and severity of this disease. With alcoholic liver damage in the later stages of cirrhosis, lymphopenia is observed, and in the earlier stages - in the clinic of alcoholic hepatitis - there is a slight decrease in the number of lymphocytes, which returns to normal values ​​a few weeks after recovery. Violation immune function may be accompanied by changes percentage different types (subpopulations) of lymphocytes or changes in the expression of certain markers of the cell surface of lymphocytes. It was found that in patients with alcoholism, the ratio of T cells carrying the CO4+ marker (“helper cells”) to T cells carrying the CD8+ marker (“cytotoxic” and “suppressor cells”) is normal or slightly increased, which is sharply distinguishes them from AIDS patients, who have a pronounced decrease in the ratio of СР4/С08.

Changes in the expression of various molecules on the surface of T-cells in patients with alcoholism are expressed in an increase in the percentage of cells with the MHC-I histocompatibility molecule, as well as in changes in adhesion proteins. These changes, taken together, are indicative of "sustained activation" of T cells. T cell activation can be observed for a long time after alcohol cessation, but the meaning of such prolonged activation is not yet fully understood (Cook, 1998).

The content of B-cells (lymphocytes producing antibodies) in patients with alcoholism without liver damage is normal or slightly reduced, while in patients with alcohol defeat liver their number is reduced significantly, despite the fact that they produce abnormally large amounts of immunoglobulins. The subpopulation composition of B cells also changes, although these changes are not as long-lasting as in the case of T cells. Functional and morphological characteristics T- and B-cells are the basis for the occurrence of disturbances in the processes of their interaction, which is important for understanding the mechanisms of inadequate production of immunoglobulins and other defects in immune regulation in patients with alcoholism. As for lymphocytes, known as natural killer cells (NKC), their number and functional activity in alcoholic patients without liver damage do not differ from the norm, provided that they abstain from alcohol for two weeks or more. In patients with steatosis or those who have recently consumed alcohol, the activity of the ECC may be increased. ECC activity is increased in alcoholic patients, despite factors such as smoking and malnutrition, which tend to inhibit ECC activity. However, in patients with alcoholic liver disease, the number and activity of EKK are significantly reduced (Cook, 1998). According to our study, the cytotoxic activity of NCC in patients with alcoholism is significantly increased in the acute phase of the withdrawal syndrome and returns to normal in remission (Gamaleya et al., 1994).

Neutrophils are white blood cells that form the first front of defense against bacteria, but also react to non-specific damage to body tissues. With alcoholic hepatitis, the number of these cells in the blood often increases, and with microscopic examination liver revealed its infiltration with neutrophils. Because these cells typically secrete powerful tissue-damaging enzymes, an increased influx of neutrophils to the liver in heavy drinkers may be one possible mechanism for liver damage. Some patients with alcoholism late stages disease, there is a significant decrease in the number of neutrophils in the blood - probably due to bone marrow suppression, which makes an additional contribution to the formation of immunosuppression. Among other changes in neutrophils in patients with alcoholism, a decrease in their migration to the area of ​​inflammation due to a weakening of chemotaxis, a decrease in the ability to adhere to vessel walls, a decrease in phagocytic activity, and intracellular killing of bacteria are described (Cook, 1998). In persons with alcoholic cirrhosis, neutrophil chemotaxis is impaired even in the absence of ethanol in the blood or recent alcohol intake. The ability of monocytes and macrophages to phagocytize bacteria and produce substances toxic to them is reduced by the action of alcohol on the cells of t uygo and in patients with alcoholism t sho. The inability of leukocytes to adhere to the walls of capillaries can lead to impaired diapedesis through the walls of blood vessels to the site of injury, while impaired phagocytosis and intracellular killing of bacteria partly explain the decrease in the ability of alcoholics to localize infection, especially if it is caused by encapsulated microorganisms.

Animal experiments have confirmed the development of immunosuppression under the influence of alcohol. Thus, in mice of the C57/B16 breed, even a short-term introduction of high doses of ethanol into the diet caused inhibition of the phagocytic activity of macrophages and a decrease in their quantitative level, as well as a decrease in the number of T-lymphocytes, mainly due to the subpopulation of T-suppressors with a simultaneous increase in the subpopulation of T- helpers, and a drop in the number of B-lymphocytes. In rats, ethanol at doses addictive, led to a decrease in the total number of lymphocytes (with an increase in the number of granulocytes) and to a sharp inhibition of the proliferative response of T- and B-lymphocytes to their stimulation with mitogens. In an experiment on white outbred rats, conducted by T.A. Naumova, it was shown that chronic alcoholization and the subsequent withdrawal period are accompanied by distinct changes in the immunocytogram: during the period of intoxication, a deficiency of T-suppressors was revealed, and in the withdrawal period, a deficiency of T-helpers and natural killers (EKK). Because one of essential functions T-suppressors - prohibition (i.e. destruction) of cell clones that synthesize antibodies to the body's own antigens, then the deficiency of these cells during alcohol intoxication is fraught with the risk of developing autoimmune complications at this time. Deficiency in the withdrawal period of T-helpers - the key cells of the specific immune response, inducing the work of all other parts of the specific immune response by means of the production of numerous cytokines, as well as the ECC responsible for the destruction of body cells affected by a virus or undergoing malignant transformation, creates high risk formation of infectious complications and promotes carcinogenesis.

Mediators of immunity - cytokines. One of the most important achievements immunology recent years is the discovery of a vast network of regulatory protein molecules called cytokines. Many types of these proteins are secreted by cells of the immune system, and changing their ratio has a pronounced effect on the function of immune cells. Alcohol has been shown to affect the production of some of these molecules. An overview of the results of their study, including data on increased levels of cytokines such as interleukin (IL-1), IL-6, IL-8, and tumor necrosis factor (TNF)-a, in patients with alcoholic liver disease, is presented in C.McClat. e1 a1. (1993). It seems clear that in these patients, blood monocytes and fixed macrophages, such as Kupffer cells in the liver, produce an excess of pro-inflammatory cytokines: IL-1, IL-6, and TNF-a. In addition, these monocytes appear to be more sensitive to lipopolysaccharide (LPS) stimulation, which also induces them to secrete TNF-α. Since TNF-α is toxic to many cells, causing ichapoptosis, it seems possible that excessive secretion of this cytokine by monocytes and Kupffer cells contributes to liver cell death. According to this hypothesis, in patients with acute alcoholic hepatitis, the prognosis is worse in case of a significant increase in the level of TNF-a in the blood serum. It has been shown that monocytes from alcoholics produce less IL-10 than cells from healthy ones, and therefore they cannot inhibit the excessive production of such a pro-inflammatory cytokine as TNF-a. However, in the lung, secretion of pro-inflammatory cytokines by LPS-stimulated alveolar macrophages appears to be reduced in many alcoholics, leading to an increased susceptibility to pneumonia.

It is also of interest to increase the level of IL-8 in alcoholism, since this cytokine causes an increase in the number of neutrophils, enhances their metabolism and chemotaxis. The level of IL-8 increases in patients with alcoholic hepatitis, and since it is also secreted by the liver, this circumstance may partly determine the increased infiltration of the liver with neutrophils in hepatitis. It has also been shown that acute exposure to alcohol on isolated human monocytes leads to stimulation of their production of IL-10 instead of IL-12 and TNF-a. This is of great importance for the severity of immunity, since IL-10 inhibits several cellular immune responses, the initiation and continuation of which depend on IL-12.

It has been suggested that the immune disorders observed in alcoholism are associated with a change in the balance between the activity of TH1 and Th2 helper cells towards the predominance of the functional activity of TP2 cells. This assumption was made on the basis of data on the detection of increased levels of immunoglobulins and immunodeficiency in persons who abuse alcohol. Reactions involving ThI cells are predominantly cellular and are most pronouncedly stimulated by IL-12 and y-interferon; while reactions involving Th2 cells are predominantly humoral (mediated by antibodies) and most effectively stimulated by IL-4, IL-5 and IL-10. The immune responses regulated by both types of helper cells depend on the activity of the antigen presenting cells. It is becoming more and more obvious that a shift in the balance between two types of helper cells in either direction leads to the development of an immunological disease. Autoimmune conditions are often characterized by an excess of Th1 reactions, while immune deficiency and allergic disorders occur with a predominance of Th2 reactions (Cook, 1998). In experiments on mice, it has been proven that alcohol consumption leads to a disruption of ThI-mediated cellular responses, while Th2-mediated antibody responses do not change or are enhanced (C. Maelenbaidhn etal., 1998). In mice immunized with T cell receptors, alcohol has also been shown to have a direct effect on presenting cells, which in turn determine which response pattern (ThI or TM2 mediated) will dominate.

Prospects for the correction of immune system disorders in patients with alcoholism. The goals of immunocorrection can be to restore the balance of T1 DN2 cells, reduce the severity of the autoimmune process, and increase the activity of immune system cells. There are a number of ways to rebalance cytokines, among which may be mentioned: administration of antibodies to certain cytokines or soluble cytokine receptors (to absorb excess cytokines without stimulating any cells); administration of cytokine receptor antagonists; application medicines, which block the production of cytokines or specific reactions; the introduction of antagonists of adhesion molecules, etc. (Cook, 1998). Many researchers have looked for ways to treat alcoholic hepatitis or pneumonia. Attempts have been made to use the granulocyte colony-stimulating factor (CSFG) to increase the number of neutrophils and improve their functional activity - both in the experiment on rats that received ethanol for a long time, and in patients with alcoholism (E.\L/.

Chapter 4. The role of opioid receptors in the pathogenesis of drug addiction and alcoholism L.F. Panchenko, S.K. Sudakov, K.G. Gurevich

Chapter 1

Chapter 8

Chapter 18

Microorganisms and bacteria are all around us. Fortunately, our immune system is designed to protect our bodies from a variety of foreign substances that can make us sick. Alcohol abuse can weaken the immune system, making our body an easier target for disease.

Knowing about the effect alcohol can have on our immune system can influence your decision to drink.

Our immune system is often compared to an army. This army protects our body from infections and diseases. Our skin and mucous membranes that line our airways and digestive tract help block bacteria from entering the body. If foreign substances somehow penetrate these barriers, our immune system enters the battle with two defense mechanisms: innate and acquired immunity.

These substances, called antigens, can enter your body and make you sick. The components of innate immunity include:

• Leukocytes. These cells form your first line of defense against infections. They quickly surround and absorb foreign particles.
• natural killers are special white blood cells that detect and destroy cells infected with cancer or viruses.
• Cytokines-leukocytes produce these chemical substances right in the infected area. Cytokines trigger immune responses such as expansion blood vessels and increased blood flow to the affected area. They also call more white blood cells to the infected area.

Acquired immunity kicks in after you are first exposed to an infection. The next time you encounter the same infection, your adaptive immunity will deal with it even faster and more effectively than it did the first time. Components of acquired immunity include:

• T-lymphocytes– T cells enhance the effects of leukocytes by attacking specific foreign substances. T cells can identify and destroy large numbers of bacteria and viruses. They can also destroy infected cells and secrete cytokines.
• B-lymphocytes B cells produce antibodies that fight harmful substances by joining them and marking them for others immune cells.
• Antibodies- After B cells encounter antigens, they produce antibodies. These are proteins that target specific antigens and then remember how to deal with them.

Risks

Alcohol suppresses both innate and acquired immunity. Chronic use of alcoholic beverages reduces the ability of white blood cells to effectively absorb and pathological bacteria.

Drinking too much alcohol also interferes with the production of cytokines, which can cause your body to produce too much or not enough of these chemical inflammatory mediators.

An excess of cytokines can damage your tissues, while a lack of them leaves the body vulnerable to infections.

Chronic alcohol consumption also suppresses T-cell production and can disrupt the ability of natural killer cells to attack cancer cells. This decrease in function makes you more vulnerable to bacteria and viruses and less able to destroy malignant cells.

With a weakened immune system, chronic drinkers are more likely to develop infectious diseases such as pneumonia and tuberculosis than people who don't drink as much. There is also evidence that alcohol disrupts the immune system with increased susceptibility to HIV infection. HIV develops faster in chronic drinkers who already have the virus.

Drinking too much alcohol on one occasion can also weaken your immune system. Drinking prior to intoxication can slow down the body's ability to produce cytokines that protect the body from infections. Without these inflammatory responses, your body's ability to protect itself from bacteria is greatly impaired. A recent study showed that slowing down the production of cytokines can impair your ability to fight infections within 24 hours of drinking alcohol.

Still looking for the good side

On the this moment, scientists don't know whether abstinence, reduced drinking, or other measures can help reverse alcohol's effects on the immune system.

However, it is important to remember that avoiding alcohol helps to minimize the burden on your immune system, especially if you are fighting a viral or bacterial infection.

Surgical intervention usually causes the induction of immunodeficiency states in the body, accompanied by the formation of purulent complications. The reason is that, firstly, the operation is performed for purulent pathology, and therefore there is a risk of its spread; secondly, the operation is mental and physical stress causing immunosuppression; thirdly, surgical interventions for severe somatic diseases affecting the vital important organs, accompanied by the use of many patients medicines with suppressive properties (diabetes mellitus, chronic hepatitis, uremia). The described situations are exacerbated by the suppressive effect on the immune system of anesthesia, anesthesia drugs.

After surgery, there is a decrease in the content of T-lymphocytes in the peripheral blood, suppression of their function, a change in the severity of the synthesis of IL-4, IL-10, TFR, PGE; the function of natural killers is inhibited and the number of T-helpers is reduced.
So much so that there is an activation of Tx2-lymphocytes with a parallel decrease in Txl activity. Removal of peripheral organs of the immune system causes its significant disorders. So, with tonsillectomy, there is atrophy of the thymus gland, a threefold increase in the frequency of chronic nasal diseases, an eightfold increase in the incidence of external paranasal sinuses, a tenfold increase in acute respiratory infections, and a twelvefold increase in pharyngitis. The revaccination effect on viral vaccines, for staphylococcal toxoid. The production of IgG and IgA, interferon, phagocytic activity of leukocytes in oral cavity, the formation of lysozyme, antiviral and anti-poliomyelitis antibodies is significantly reduced. Healthy people with tonsils removed do not show any changes immune status on the contrary, some stimulation is observed.

However, during the formation of pathological processes, the severity of immune disorders in such patients is significantly greater than in patients with preserved peripheral lymphoid organ.
Appendectomy causes some increase in morbidity and severity intestinal infections, drop in expression protective factors in the intestinal tube, a violation of colony resistance in the large intestine, an increase in the risk of dysbacteriosis. After splenectomy, the level of IgM in the blood decreases in patients, the mechanism of complement activation is disrupted, the content of other classes of immune globulins, the ability to synthesize AT of different classes, the activity of natural killers, and the response of lymphocytes to mitogens decrease. The function of complement and other serum components with opsonizing properties suffers. However, in some patients after surgery for removal of the spleen in abdominal cavity splenic tissue is regenerated.

Not only surgical, but also any other traumatic injuries have a depressive effect on the immune system, primarily due to stress and related hormonal changes.
As a rule, with severe injuries, suppression of the T- and B-links of immunity, the function of neutrophils occurs. Given this, for preoperative preparation and immediately after surgery, it is recommended to use immunocorrective agents: thymus preparations, diucifon, dapsone, sodium nucleinate, polysaccharide preparations, myelopide, and small immunocorrectors. The risk of developing immune disorders after surgery is:
- the presence of severe concomitant diseases: HB3JI, especially asthma, ischemia, cardiosclerosis, rheumatic heart disease, endocrine (diabetes, CAT), diseases urinary system, rheumatism, peptic ulcer, pancreatitis, gastritis, liver damage, colitis, tumors;
- any chronic diseases with long-term medication, especially antibiotics, corticosteroids, cytostatics, psychotropic drugs;
- the presence of blood groups in patients with A (P) or AB (IV) with an increase in the risk of immunodeficiencies by 3 and 2 times, respectively;
- a history of frequent infectious (including "dormant") diseases;
- a history of surgical interventions, especially for appendicitis, gynecological lesions, purulent infections of soft tissues, cholelithiasis;
- the presence of allergic reactions in the patient and blood transfusions.

Age: favorable age 17-40 years; an increase in immune disorders by 12% in patients aged 41-60 years, by 29-40% - older than 60 years. The urgency / urgency of the operation increases the risk of developing immunodeficiency by 2.3-3 times. The duration of hospitalization provokes the risk of developing immunodeficiency, it is optimally desirable to stay in the hospital for 3-5 days. In smoking patients, an increase in the absolute and relative content of T-lymphocytes and, especially, y-lymphocytes, which are a population with suppressive properties, is registered (in comparison with people who do not use tobacco). The absorption activity of phagocytes was stimulated only in elderly people (50-64 years old) with a long history of having bad habit. Cell-mediated reactivity (in the PTMJI and RPPL tests) changed less, but with strong exposure harmful factor went down.

With prolonged use of alcohol, the content of the total number of leukocytes, T-lymphocytes, especially in men, T-cells endowed with suppressor properties, significantly increases. RBTL does not change significantly when large doses The intake of alcohol suppresses the absorption capacity of phagocytes. The concentration of IgG increases. In general, changes in the components of immune reactivity under the influence of these factors in women are less pronounced. This is most likely due to the lower frequency of smoking and drinking alcohol. The general stimulation of the T-link of immunity is due to the predominant activation of the T-suppressor link of immunity, which can be considered as an endogenous risk factor for oncological and other diseases.

Currently, it is believed that in the pathogenesis of chronic alcoholism, a significant role is played by disorders that occur in the body as a result of the inclusion of exogenous alcohol and its metabolic products in metabolic processes. These disorders are present in various physiological systems body, including the immune system. It is believed that at chronic alcoholism formed secondary immunodeficiency by T-dependent type, which is based on alcohol-induced liver damage ( alcoholic hepatitis and alcoholic cirrhosis). However, this point of view is one-sided, does not take into account the peculiarities of changes in other parts of the immune system and the nature of alcohol abuse. A general conclusion can be drawn from this section:
- chronic alcoholism, which occurs without laboratory and clinical signs of liver pathology, is characterized by an increase in the level of B-lymphocytes and a decrease in the concentration of T-cells;
- the increase in the number of B-lymphocytes in the blood is most pronounced in patients with a relatively short duration of the disease and with an unsystematic nature of alcohol consumption;
- a decrease in the number of T-lymphocytes in the blood is observed in patients in remission. Alcoholic withdrawal syndrome accompanied by an increase in the content of T-lymphocytes in comparison with the indicators in the post-withdrawal period and in remission. This reflects the degree of preservation of the adaptive capabilities of the organism in chronic alcoholism;
- higher T-cell counts correspond to clinical manifestations high tolerance to alcohol, which must be taken into account when assessing the immune status of patients;
- in the population of peripheral blood lymphocytes of patients with alcoholism, to a greater extent than normal, there are T-cells with abnormal properties. Their ability to spontaneous rosette formation (a test for the functional activity of membrane receptors) is weakly inhibited by trypsin and does not change under the influence of histamine;
- prolonged intoxication with ethanol inhibits the primary immune response to thymus-dependent antigens;
- a relationship has been established (under conditions of acute and chronic alcohol intoxication) between the number of T-B-lymphocytes and the level of activity of alcohol dehydrogenase and a-succinate dehydrogenase of the liver. An increase in the number of T-B-lymphocytes is noted with increased activity alcohol dehydrogenase and a-succinate dehydrogenase;
- a decrease in the content of the main populations of lymphoid cells - with a decrease in the activity of these enzymes. Supposed direct action ethanol on lymphocyte receptors;
- Violations occur in the phagocytic link of immunity. As the duration of alcoholization increased, patients experienced a decrease in the level of monocytes, suppression of their functional activity, which coincided with a decrease in the content of lysozyme and complement in the blood serum; immune reactions - there is a violation of the regulatory function of T-suppressors, damage to the receptor apparatus of macrophages and epithelium gastrointestinal tract. These processes are accompanied by increased penetration into internal environment organism of intestinal toxins, food allergens and other factors that “irritate” the B-link of immunity. As a result, humoral immunity becomes uncontrollable due to the excessive formation of immune globulins of different classes. To this it should be added that with a decrease in the detoxifying function of the liver, the destruction of immune proteins slows down, which contributes to their accumulation in the blood serum, and a direct toxic effect of ethanol on metabolism develops. various cells. In some cases, the effect of alcohol is mediated through the neurotransmitters of dopaminergic structures, neurohormones and cyclic nucleotides.

The presented information justifies the appointment of persons suffering from chronic alcoholism, modulators (stimulators) of the T-link of immunity, as well as the use of anabolic hormones, amino acids (retabolil, L-aspartic and glutamic acids).

Brain is the most active consumer of energy. The negative effect of alcohol on the brain is associated with impaired access of oxygen to neurons as a result of alcohol intoxication.

Alcoholic dementia, which develops in connection with prolonged alcohol use, leads to social death of brain cells. The harmful effects of alcohol affect all systems of the human body (nervous, circulatory, digestive).

Doctors of various specialties pay close attention to both the condition internal organs with alcoholism, and to those changes in their activities that are caused by moderate alcohol consumption. The role of alcohol in the development of many diseases has so far often remained disguised. This significantly reduced the effectiveness of therapeutic measures; currently, the detrimental role of alcoholism in various acute and chronic diseases has been proven.

Diseases of cardio-vascular system occupy a leading place in the structure of mortality. Under the influence of alcohol, the heart muscle is affected, which leads to serious illnesses and increased mortality.

An increase in the volume of the heart is found in x-ray examination. "Alcoholic cardiomyopathy" does not develop in all patients suffering from chronic alcoholism, and at the same time it can occur in patients with relatively little alcohol experience.

Even in healthy people, after a large dose of alcohol, heart rhythm disturbances may appear, but gradually they spontaneously disappear.

Alcohol abuse contributes to the development and progression hypertension, coronary heart disease, is often the direct cause of heart attacks.

Breath is synonymous with life. Breathing refers to inhalation and exhalation, which alternate regularly. The respiratory process consists of four stages, violation of any of them leads to a serious respiratory disorder. In patients suffering from the first stage of chronic alcoholism, there is some stimulation of the function external respiration: the minute volume of breathing increases, breathing is rapid.

As the disease progresses, breathing worsens. May occur various diseases: Chronical bronchitis, tracheobronchitis, emphysema, tuberculosis. Alcohol is often combined with tobacco. When these two poisons act simultaneously, they harmful effect increases even more.

Tobacco smoke damages the structure of alveolar macrophages - cells that protect the lung tissue from organic and mineral dust, neutralize microbes and viruses, destroy dead cells. Tobacco and alcohol pose serious health risks.

Gastrointestinal pathology. Patients with chronic alcoholism often complain of disturbances in the activity of the gastrointestinal tract, since the gastric mucosa primarily perceives the toxic effects of alcohol. Examination reveals gastritis, peptic ulcer stomach and duodenum. With the development of alcoholism, the function is impaired salivary glands. Other pathological abnormalities also develop.

Liver occupies a special position among the organs of the digestive system. This is the main chemical laboratory of the body, which performs an antitoxic function, participates in almost all types of metabolism: protein, fat, carbohydrate, water. Under the influence of alcohol, liver function is impaired, which can lead to cirrhosis of the liver.

The majority of alcoholics have impaired excretory functionkidneys. There are malfunctions in the work of the entire hypothalamic-pituitary-adrenal system, therefore, the regulation of the activity of the kidneys is disturbed. Alcohol has a detrimental effect on the delicate renal epithelium, significantly disrupting the activity of the kidneys.

With alcoholism suffers not only central, but also peripheral nervous system. Manifestations are very diverse: mental abnormalities in the form of hallucinations, numbness of body parts, muscle cramps, sometimes severe weakness in the limbs, as if "cotton legs". Often, paralysis of individual muscle groups develops, mainly lower extremities. With abstinence from alcohol, these symptoms may go away.

Alcohol has a detrimental effect on immune system human, violates the processes of hematopoiesis reduces the production of lymphocytes. Alcohol contributes to the development of allergies.

The use of alcohol leaves a significant imprint on the activity of the internal organs and this means that we should give up a glass of dry wine, replacing it with a glass of juice or eating a few fruits.

Alcohol renders bad influenceon the endocrine glands and primarily on the sex glands. A decrease in sexual function is observed in 1/3 of alcohol abusers and in patients with chronic alcoholism. As a result of "alcoholic impotence" in men, various functional disorders of the central nervous system(neurosis, reactive depressions etc.). In women under the influence of alcohol, menstruation stops early, the ability to bear children decreases, and toxicosis of pregnancy is more often observed.

Regular use of alcohol leads to premature old age, disability; the life expectancy of persons prone to drunkenness is 15–20 years shorter than the average.

And at what age do children learn the taste of wine?

Teachers of one of the Riga schools were interested in how high the awareness of students in the field of alcoholic beverages is. It turned out that the boys knew the names of almost 100 brands of wine, and the girls - half as much. They began to specify at what age the initiation to alcohol occurred, and received an alarming picture:

- for tenth-graders, it began at the age of 13-14;

- for eighth graders - at 7-8 years old;

– and fourth-grade students got to know his taste when they were 4-5 years old.

And everyone tasted alcohol for the first time in the family circle!!!

75% of students in grades 8-10 drink alcohol on holidays and family celebrations. In most cases, the first glass is drunk with the blessing of relatives. Thus, cadres of future alcoholics are often prepared in the family. Take an alcohol addiction test

Some habits and events that are constantly present and occurring in our lives imperceptibly, but consistently and methodically destroy our brain.

Below 10 things that also negatively affect the brain:

Chronic sleep deprivation

This phenomenon, familiar to everyone, becomes global problem. According to WHO, over the past 100 years, a person began to sleep on average 20% less. Chronic sleep deprivation is fraught with the fact that in the actual state of wakefulness various sections the brain enters the slow-wave sleep phase. At this time, a person “freezes” at one point, becomes dispersed, fine motor skills deteriorate. Regular lack of sleep leads to the death of brain cells.

Lack of breakfast

Skipping a morning meal negatively affects the performance and tone of a person during the day. This seems obvious, but it's not so much about consuming the energy the body needs, but about the fact that the lack of breakfast lowers blood sugar levels. And this, in turn, reduces and makes it difficult to enter the brain nutrients.

Too much sugar

The previous paragraph explains why eating sweets, especially dark chocolate, is recommended for productive brain function. However, excessive amounts of sugar cause problems with protein and nutrient absorption. The result is the same as with low blood sugar: the brain simply does not receive nutrients.

Stress

Strong psycho-emotional stress leads to a break in connections between neurons and makes it difficult to understand cause-and-effect relationships and the sequence of events. Associated with this is a strong nervous excitement and a feeling that everything is falling out of hand. Accumulated stress impairs memory and reduces intellectual potential.

Antidepressants and sleeping pills

The problem of the strong drug craze is most relevant in the United States, where such drugs are prescribed very easily. The use of sleeping pills and popular antidepressants like Xanax can impair memory up to amnesia, cause dementia and obsessive suicidal thoughts.

Smoking

Speaking of negative influence smoking on the body, the first thing that comes to mind is the image of black lungs and damaged teeth. At the same time, little is said about how cigarettes affect the brain: nicotine constricts its blood vessels. However, cognac expands back. In addition to problems associated with a lack of nutrients in the brain, this greatly increases the risk of Alzheimer's disease.

- a disease in which there is a physical and mental dependence on alcohol. Accompanied by increased craving for alcohol, inability to regulate the amount of alcohol consumed, a tendency to binge drinking, the occurrence of a pronounced withdrawal syndrome, a decrease in control over one's own behavior and motivations, progressive mental degradation and toxic damage internal organs. Alcoholism is an irreversible condition, the patient can only completely stop drinking alcohol. Drinking the smallest doses of alcohol even after long period abstinence causes a breakdown and further progression of the disease.

Ethanol metabolism and dependence development

Main component alcoholic beverages- ethanol. Small amounts of this chemical compound are part of the natural metabolic processes in the human body. Normally, the ethanol content is not more than 0.18 ppm. Exogenous (external) ethanol is rapidly absorbed into digestive tract enters the bloodstream and affects nerve cells. The maximum intoxication occurs 1.5-3 hours after drinking alcohol. When taking too much alcohol, a gag reflex occurs. As alcoholism develops, this reflex weakens.

About 90% taken alcohol oxidized in cells, broken down in the liver and excreted from the body in the form of end products of metabolism. The remaining 10% is excreted unprocessed through the kidneys and lungs. Ethanol is excreted from the body within about a day. In chronic alcoholism, the intermediate products of ethanol breakdown remain in the body and have a negative effect on the activity of all organs.

Development mental addiction in alcoholism due to the effect of ethanol on the nervous system. After taking alcohol, a person feels euphoria. Anxiety is reduced, the level of self-confidence increases, it becomes easier to communicate. Basically, people are trying to use alcohol as a simple, affordable, fast-acting antidepressant and stress reliever. As a “one-time help”, this method sometimes really works - a person temporarily relieves tension, feels satisfied and relaxed.

However, the intake of alcohol is not natural and physiological. Over time, the need for alcohol increases. A person, who is not yet an alcoholic, begins to drink alcohol regularly, without noticing gradual changes: an increase in the required dose, the appearance of memory lapses, etc. When these changes become significant, it turns out that psychological dependence is already combined with physical dependence, and one should independently refuse drinking alcohol is very difficult or almost impossible.

Alcoholism is a disease closely related to social interactions. At the initial stage, people often drink alcohol due to family, national or corporate traditions. In a drinking environment, it is more difficult for a person to remain a teetotaler, since the concept of “normal behavior” is shifting. In socially successful patients, alcoholism may be due to a high level of stress at work, the tradition of "washing" successful transactions, etc. However, regardless of the root cause, the consequences of regular alcohol intake will be the same - alcoholism will occur with progressive mental degradation and deterioration in health.

Consequences of drinking alcohol

Alcohol has a depressant effect on the nervous system. At first, euphoria occurs, accompanied by some excitement, a decrease in criticism of one's own behavior and ongoing events, as well as a deterioration in coordination of movements and a slowdown in reaction. Subsequently, excitement is replaced by drowsiness. When taking large doses of alcohol, contact with the outside world is increasingly lost. There is a progressive distraction of attention in combination with a decrease in temperature and pain sensitivity.

expressiveness movement disorders depends on the degree of intoxication. In severe intoxication, a gross static and dynamic ataxia is observed - a person cannot maintain vertical position body, his movements are highly uncoordinated. Violated control over the activity of the pelvic organs. When taking excessive doses of alcohol, weakening of breathing, cardiac disturbances, stupor and coma may occur. Possible fatal outcome.

In chronic alcoholism, typical lesions of the nervous system due to prolonged intoxication are noted. During the exit from hard drinking, alcoholic delirium (delirious tremens) may develop. Somewhat less frequently, patients suffering from alcoholism are diagnosed with alcoholic encephalopathy (hallucinosis, delusions), depression and alcoholic epilepsy. Unlike delirium tremens, these conditions are not necessarily associated with an abrupt cessation of drinking. In patients with alcoholism, a gradual mental degradation, narrowing the range of interests, cognitive impairment, decreased intelligence, etc. In the later stages of alcoholism, alcoholic polyneuropathy is often observed.

To typical violations from the gastrointestinal tract include pain in the stomach, gastritis, erosion of the gastric mucosa, as well as atrophy of the intestinal mucosa. Possible acute complications in the form of bleeding caused by gastric ulceration or violent vomiting with mucosal tears in the transitional section between the stomach and esophagus. because of atrophic changes The intestinal mucosa in patients with alcoholism worsens the absorption of vitamins and microelements, metabolism is disturbed, beriberi occurs.

Liver cells in alcoholism are replaced connective tissue develops cirrhosis of the liver. Acute pancreatitis, which occurred against the background of alcohol intake, is accompanied by severe endogenous intoxication, may be complicated by acute renal failure, cerebral edema and hypovolemic shock. Mortality in acute pancreatitis ranges from 7 to 70%. Characteristic disorders of other organs and systems in alcoholism include cardiomyopathy, alcoholic nephropathy, anemia, and immune disorders. Alcoholics are at increased risk of developing subarachnoid hemorrhages and some forms of cancer.

Symptoms and stages of alcoholism

There are three stages of alcoholism and a prodrome - a condition when the patient is not yet an alcoholic, but regularly consumes alcohol and is at risk of developing this disease. At the prodrome stage, a person willingly takes alcohol in the company and, as a rule, rarely drinks alone. The use of alcohol occurs in accordance with the circumstances (a celebration, a friendly meeting, a rather significant pleasant or unpleasant event, etc.). The patient can stop taking alcohol at any time without suffering any unpleasant consequences. He has no desire to continue drinking after the event is over and easily returns to normal sobriety.

The first stage of alcoholism accompanied by increased craving for alcohol. The need for alcohol resembles hunger or thirst and is aggravated in adverse circumstances: quarrels with loved ones, problems at work, an increase in the overall level of stress, fatigue, etc. If an alcoholic patient does not manage to drink, he is distracted and cravings for alcohol temporarily decreases until the next adverse situation. If alcohol is available, the alcoholic drinks more than the prodrome. He tries to achieve a state of pronounced intoxication by drinking in company or drinking alcohol alone. It is more difficult for him to stop, he strives to continue the "holiday" and continues to drink even after the end of the event.

Characteristic features of this stage of alcoholism are the extinction of the gag reflex, aggressiveness, irritability and memory lapses. The patient takes alcohol irregularly, periods of absolute sobriety may alternate with isolated cases of alcohol consumption or be replaced by binges lasting several days. Criticism of one's own behavior is reduced even during the period of sobriety, a patient with alcoholism tries in every possible way to justify his need for alcohol, finds all sorts of "worthy reasons", shifts the responsibility for his drinking to others, etc.

The second stage of alcoholism manifested by an increase in the amount of alcohol consumed. A person takes more alcohol than before, while the ability to control the intake of ethanol-containing drinks disappears after the first dose. On the background abrupt rejection from alcohol there is an abstinence syndrome: tachycardia, increased blood pressure, sleep disturbances, trembling fingers, vomiting when taking liquids and food. Perhaps the development of delirium tremens, accompanied by fever, chills and hallucinations.

The third stage of alcoholism manifested by a decrease in tolerance to alcohol. To achieve intoxication, it is enough for a patient suffering from alcoholism to take a very small dose of alcohol (about one glass). When taking subsequent doses, the state of the patient with alcoholism practically does not change, despite the increase in the concentration of alcohol in the blood. There is an uncontrollable craving for alcohol. Drinking alcohol becomes constant, the duration of binges increases. When you refuse to take ethanol-containing drinks, delirium tremens often develops. Mental degradation is noted in combination with pronounced changes in internal organs.

Treatment and rehabilitation for alcoholism

Prognosis for alcoholism

The prognosis depends on the duration and intensity of alcohol intake. At the first stage of alcoholism, the chances of a cure are quite high, but at this stage, patients often do not consider themselves alcoholics, so they do not seek treatment. medical care. In the presence of physical dependence, remission for a year or more is observed in only 50-60% of patients. Narcologists note that the likelihood of long-term remission increases significantly with the active desire of the patient to refuse to take alcohol.

The life expectancy of patients suffering from alcoholism is 15 years less than the average for the population. The cause of death is typical chronic diseases and acute conditions: alcoholic delirium, stroke, cardiovascular insufficiency and cirrhosis of the liver. Alcoholics are more likely to have accidents and are more likely to commit suicide. Among this population group, there is a high level of early disability due to the consequences of injuries, organ pathology and severe metabolic disorders.