concanavalin-a and Alcoholism

Altered immunity is commonly associated with alcoholism. However, few studies have contrasted alcoholism per se with effects of the medical sequelae or comorbidities of alcoholism on the immune system. We previously found few differences in lymphocyte subsets, mitogen response, granulocytic phagocytosis, or natural killer cell activity when we compared healthy urban alcohol-dependent individuals with community control subjects. To begin to explore the role of medical factors, 11 alcohol-dependent persons derived from the same clinical population but showing mild medical abnormalities (AMMAs), primarily abnormal liver function test results, were compared with the previously described 44 alcohol-dependent persons without medical dysfunctions and 34 nonabusing community persons. The AMMAs had lower numbers of CD45RA + inducer-suppressor/naive cells (P <.02) and HLA-DR+-activated T cells (P <.04) compared with findings for nonabusers and higher percentages of circulating CD56 + natural killer cells (P <.03). Mitogen responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen; natural killer cell activity; and granulocyte functions did not differ across groups. The AMMAs reported higher alcohol consumption than that reported by the other groups. The findings seem to indicate that mild medical conditions, or conditions linked to abnormal liver function test results, are associated with some of the immune alterations reported in alcohol-dependent persons. Immune changes, even among chronically alcohol-dependent persons, may occur along a continuum associated with total alcohol exposure and intercurrent physiologic abnormalities. Clinical studies may need to control for such mild abnormalities when investigating alcohol-immune relationships, and clinical interventions may be especially important for alcohol-dependent individuals who show early signs of compromised health.

Topics: Adolescent; Adult; Aged; Alcoholism; CD56 Antigen; Concanavalin A; Female; Granulocytes; Health Status; HLA-DR Antigens; Humans; Immunity; Killer Cells, Natural; Leukocyte Common Antigens; Leukocyte Count; Liver Diseases, Alcoholic; Lymphocyte Count; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Seventy newly diagnosed Caucasian male patients with head and neck squamous cell carcinomas (HNSCC) were included in the study. All patients were less than 80 years of age, with no cachexia or auto-immune disease, and they were not taking immuno-active medications. Monocytes from these patients were cultured in vitro and supplemented with autologous serum under ex vivo conditions or cultured with serum-free medium. Comparison was made to monocytes from 59 patients with benign HN diseases. Similar physical activity levels prior to testing as well as a minimum stress load were ensured in both groups. Increased monocyte supernatant levels were determined under ex vivo conditions of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha, but not of interleukin-12 (IL-12) with endotoxin stimulated monocytes of HNSCC patients compared to control conditions. Increased monokine levels were not present with mononuclear cell cultures stimulated with a T-cell general stimulatory agent or with purified monocytes not specifically stimulated. With endotoxin-stimulated monocytes under in vitro conditions, an increased supernatant was shown for TNF-alpha, but not IL-6. With serum from the different patients cultured with monocytes employed from a healthy control, no difference between the groups was shown in the IL-6 and TNF-alpha response to endotoxin stimulation. The differences in IL-1 beta and TNF-alpha, but not IL-6 levels were differentiated statistically from the smoking and alcohol histories of the patients. These findings suggest that the function of monocytes in general, and thus possibly all mononuclear phagocyte system cells in HNSCC patients, are altered.

Topics: Alcoholism; Carcinoma, Squamous Cell; Cell Movement; Concanavalin A; Head and Neck Neoplasms; Humans; Interleukin-1; Interleukin-12; Interleukin-6; Leukocytes, Mononuclear; Male; Personality Inventory; Retrospective Studies; Smoking; Tobacco Use Disorder; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Topics: Alcoholism; Animals; Blood; Concanavalin A; Lymphocyte Activation; Swine; Swine, Miniature; T-Lymphocytes

Ethanol inhibited the mitogen-induced initial increase in cytoplasmic free-calcium [Ca2+]i in mouse splenocytes. This effect was concentration-dependent, reversible, and observed at pharmacologically relevant concentrations (24-166mM). Other short-chain alcohols such as propanol, butanol, and pentanol also inhibited this mitogen-induced increase in [Ca2+]i. The potencies of these alcohols to produce this effect were highly correlated (r = 0.98, p less than 0.001) with their membrane/buffer partition coefficients. Analysis of mouse splenocyte subpopulations demonstrated that this effect was manifest in both B and T lymphocytes. Within T lymphocyte subpopulations, both CD4+ and CD8+ T cells were affected. These results suggest that the inhibition of [Ca2+]i increase may be an early event mediating ethanol-induced immunosuppression and that this may be a predisposing factor to infection and malignancies associated with alcoholism.

Topics: Alcoholism; Animals; B-Lymphocytes; Calcium; CD4-Positive T-Lymphocytes; Concanavalin A; Ethanol; Flow Cytometry; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Spleen; T-Lymphocytes

We have investigated the effect of prenatal exposure to ethanol on the extent of binding and surface distribution of the lectin concanavalin A (con A) on rat cortical astrocytes during the periods of proliferation and differentiation in primary culture. The enzymatic activity of the plasma membrane glycoprotein 5'-nucleotidase was also assessed. The cells were obtained from control fetuses (no exposure to ethanol) and from fetuses prenatally exposed to ethanol. The main findings were: 1) both proliferating and differentiating control astrocytes showed two distinct types of surface con A receptors that could correspond to high- and low-affinity binding sites; 2) the extent of con A binding was greater in mature than in proliferating control cells; 3) the distribution of con A on cell surface components changed with differentiation; 4) the activity of 5'-nucleotidase showed a substantial increment during the period of differentiation; and 5) prenatal exposure to ethanol clearly decreased the ability of astrocytes to bind con A, altered the surface distribution of the receptors for this lectin, and decreased the activity of 5'-nucleotidase. These effects were more marked in proliferating cells. In conclusion, it is shown that the extent of con A labeling and the activity of 5'-nucleotidase in astrocytes are dependent on the stage of cell differentiation and that prenatal exposure to ethanol alters the plasma membrane structure of these cells during development.

Topics: 5'-Nucleotidase; Alcoholism; Animals; Astrocytes; Biomarkers; Cells, Cultured; Cerebral Cortex; Concanavalin A; Disease Models, Animal; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Fetus; Membrane Glycoproteins; Nerve Tissue Proteins; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Receptors, Concanavalin A

Increase in serum ferritin, which occurs in 40 to 70% of chronic alcoholics, remains poorly understood. We tested the hypothesis which links hyperferritinemia in chronic alcoholism not only to ferritin release from damaged liver cells, but also to increased ferritin secretion. Fifty-eight chronic alcoholic patients hospitalized for alcohol withdrawal were subdivided into three groups according to liver damage. Their serum levels of ferritin and ferritin bound to concanavalin A (ferritin Con A, which represents glycosylated, i.e., secreted ferritin) were measured serially on days 1, 7, and 11 of withdrawal and compared with a control group. The results were: (1) Total serum ferritin increased in alcoholics. Both free and Con A ferritins increased in equal proportions, the ferritin Con A to total ferritin ratio remaining unchanged. The increase was dependent on liver disease, as both free and Con A ferritins increased significantly with the severity of liver illness. Serum ferritin levels were related to iron status: it correlated with hepatic iron concentration (obtained in 19 patients); however, high ferritin values were not related to the degree of iron overload, which remained low. Finally, there was no correlation between serum ferritin and the average of alcohol consumption. (2) Both free and Con A ferritin decreased by about 40% during alcohol withdrawal. In conclusion, we have demonstrated that (1) total serum ferritin is increased in chronic alcoholism and (2) that this ferritin increase is due in part to an increase in ferritin Con A, proof of the induction of ferritin secretion by alcohol in humans.

Topics: Adult; Alanine Transaminase; Alcohol Withdrawal Delirium; Alcoholism; Aspartate Aminotransferases; Blood Proteins; Concanavalin A; Female; Ferritins; gamma-Glutamyltransferase; Glycated Serum Proteins; Glycoproteins; Humans; Liver Function Tests; Male; Prospective Studies; Receptors, Concanavalin A

Chronic alcoholics constitute a small but significant subgroup of burned patients. The effects of chronic alcohol exposure on immune function in burned patients has not to our knowledge been studied. This study was designed to determine the effect of chronic alcohol exposure before burn injury on immune function after injury in rats. Immune function assessed by in vivo chemotaxis and responsiveness of non-adherent splenocytes to both a T-cell mitogen, concanavalin A, and a B-cell mitogen, lipopolysaccharide, was measured at 4 days after a 20% BSA full-thickness burn injury and/or gavage of 2.4 gm/kg/day of ethanol for 14 days. Chronic ethanol ingestion before burn injury produced significant suppression in chemotaxis and response to lipopolysaccharide but not in response to concanavalin A. These results suggest that chronic alcohol exposure before injury can contribute to further impaired immune function after injury, and may lead to increased susceptibility to infection and increased mortality.

Topics: Alcoholism; Animals; Burns; Cells, Cultured; Chemotaxis, Leukocyte; Concanavalin A; Lipopolysaccharides; Male; Rats; Rats, Inbred Strains; Spleen

The microheterogeneity profile of human serum transferrin from normal and alcoholic subjects was investigated qualitatively and quantitatively by means of Concanavalin A crossed affinity immunoelectrophoresis and an image analysis program. Differences in amounts of nonreacting transferrin molecules were found, suggesting an increase in triantennary glycosylation of transferrin from alcoholics compared with normal individuals. The increased amount of a highly retarded fraction in crude sera from alcoholics was demonstrated to be artefactual, probably due to entrapment or coprecipitation as the fraction disappeared after repeating the analysis with immunosorbent-purified transferrin. In conclusion, affinity electrophoresis represents a simple approach for demonstration of variations in the neutral monosaccharides of glycans and can discriminate between transferrin from alcoholics and normal individuals.

Topics: Adult; Aged; Alcoholism; Animals; Carbohydrate Conformation; Concanavalin A; Evaluation Studies as Topic; Female; Humans; Immunoelectrophoresis; Immunoelectrophoresis, Two-Dimensional; Isomerism; Male; Middle Aged; Polysaccharides; Rabbits; Transferrin

Concanavalin A-induced lymphocyte proliferation was studied in 25 patients with alcoholic hepatitis or compensated alcoholic cirrhosis. Nine alcoholics without evidence of liver disease were also evaluated. A nonlinear correlation equation, which was natural logarithmic, was applied to individual dose-response proliferation curves and permitted comparisons between patient groups and controls. The proliferative response in all patient groups was significantly lower when compared to healthy controls and was independent of the presence or absence of liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effects of alcohol on the immune system rather than to the associated liver disease.

Topics: Alcoholism; Concanavalin A; Female; Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Function Tests; Lymphocyte Activation; Male

To evaluate the influence of chronic alcohol consumption on the cellular immune system in man, we investigated the immune response to seven intradermally applied common antigens and in vitro stimulation of peripheral lymphocytes by Phytohemagglutinin A and concanavalin A in chronic alcoholics with (n = 15) and without (n = 15) liver disease. The results suggest that the diminished cellular immune response in chronic alcoholics is not primarily a direct sequel to alcohol consumption; it is more likely that the impaired immune response is linked to severity of the liver damage itself and to malnutrition.

Topics: Adult; Aged; Alcoholism; Concanavalin A; Female; Humans; Immunity, Cellular; Intradermal Tests; Liver Diseases, Alcoholic; Lymphocyte Activation; Male; Middle Aged; Nutrition Disorders; Phytohemagglutinins

Chronic alcoholics are more susceptible to infection and have increased incidences of certain types of carcinomas. One explanation for this may be suppressed immune responses secondary to ethyl alcohol consumption. This project was initiated to study the effect of ethyl alcohol on lymphocyte responses in vitro by monitoring tritiated thymidine uptake. Lymphocytes were incubated in the presence of phytohemagglutinin-P, concanavalin A, and pokeweed mitogen. The response of normal lymphocytes was noted after mitogen stimulation in the presence of ethyl alcohol in graded doses. Ethyl alcohol levels greater than or equal to 50 mg/dL suppressed tritiated thymidine uptake of normal lymphocytes for phytohemagglutinin-P and concanavalin A. Since ethyl alcohol exposure in concentrations consistent with blood levels that may be attained during routine ingestion significantly decreased lymphocyte blastogenesis, it is speculated that chronic ethyl alcohol ingestion may alter immune surveillance sufficiently to be responsible in part for the increased incidence of infection and/or neoplasms seen in alcoholic subjects.

Topics: Adult; Alcoholism; Concanavalin A; Dose-Response Relationship, Drug; Ethanol; Female; Humans; Infections; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Neoplasms; Phytohemagglutinins; Pokeweed Mitogens; Stimulation, Chemical; Thymidine

Cellular immunity was assessed in patients with operable squamous cell cancer of the head and neck using in vivo skin tests and in vitro lymphocyte stimulation tests. An expansion of a previous study continued to show that 30 per cent of patients with T1N0M0 lesions were DNCB-negative and that with more advanced lesions there was further impairment. A similar finding was observed in the blastogenic response to phytohemagglutinin and concanavalin A but not pokeweed mitogen. Overall, 40 per cent of patients with resectable cancer had a significant depression of the blastogenic responses to conconavalin A and phytohemagglutinin. This depression ranged from 15 per cent in patients with T1N0M0 lesions to 71 per cent in those with T3N0M0 lesions. Although this depression was more severe in patients with palpable cervical node metastases, it was related more to the size of the primary tumor than to the nodes per se. An exception occurred in patients with large fixed nodes in whom the depression of lymphocyte stimulation was most severe. The absolute T-cell count was also depressed in patients with head and neck cancer. This depression parallelled the lymphocyte stimulation results with phytohemagglutinin and conconavalin A and was progressive with increasing stage of disease. A correlation exists between DNCB negativity and early recurrence and shortened survival. Clinical follow-up study is too short to assess the correlation of in vitro immune function with these clinical prognostic factors.

Topics: Alcoholism; B-Lymphocytes; Carcinoma, Squamous Cell; Concanavalin A; Dinitrochlorobenzene; Fluorescent Antibody Technique; Head and Neck Neoplasms; Humans; Immune Adherence Reaction; Immunity, Cellular; Immunologic Deficiency Syndromes; Leukocyte Count; Lymphatic Metastasis; Mitogens; Skin Tests; T-Lymphocytes

The immunologic status of 24 male patients admitted for acute alcoholic detoxification was evaluated by in vivo and in vitro parameters. In vivo reactivity, as measured by skin testing with a denovo antigen, dinitrochlorobenzene, as well as a recall antigen, tuberculin, was inact. However, both qualitative and quantitative defects were seen in vitro in the thymus-derived lymphocyte population. These defects were not seen in recovered alcoholics, that is, they appear reversible. The defects seen in the cell-mediated immunity of alcoholics may, in part, be responsible for the high incidence of head and neck cancer observed in this patient population.

Topics: Adult; Alcoholism; Bone Marrow; Carcinoembryonic Antigen; Concanavalin A; Dinitrochlorobenzene; Ethanol; Humans; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Intradermal Tests; Lectins; Liver Function Tests; Lymphocytes; Male; Middle Aged; Mitogens; Skin Tests; Thymus Gland; Tuberculin Test