Activated Lymphocytes (CD25 CD69 Cells) and Decreased CD19 Cells in Well-Nourished Chronic Alcoholics without Ethanol-Related Diseases (original) (raw)
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Immune function alcoholism: a controlled study. Alcohol Clin Exp Res 17:279–283
1993
Several studies have shown an increased risk for infection and cancer in alcoholic patients. The mechanisms for such observations remain largely unknown. In an effort to investigate the possibility of immunological dysfunction In alcoholism, we studied three immune parameters in 47 hospitalized chronic alcoholic patients and 47 age-and sex-matched normal controls. The immune measures were: (1) lymphocyte phenotyping, with estimates of percentages of T cells, B cells, T helpers, T suppressors, natural killer (NK) cells, and cells carrying the activation markers IL2R1 and 12; (2) NK cell activity; and (3) lymphokine-activated killer cell activity. Results indicate a signif-icant increase in the IL2R and l2 lymphocyte markers in alcoholic patients compared with matched controls. We also found a nonsig-nificant trend for a decrease in the percentage of suppressor T cells in the alcoholic group, as well as a trend for a negative correlation between the percentage of T suppressor cells an...
Immune Function in Alcoholism: A Controlled Study
Alcoholism: Clinical and Experimental Research, 1993
Several studies have shown an increased risk for infection and cancer in alcoholic patients. The mechanisms for such observations remain largely unknown. In an effort to investigate the possibility of immunological dysfunction In alcoholism, we studied three immune parameters in 47 hospitalized chronic alcoholic patients and 47 ageand sex-matched normal controls. The immune measures were: (1) lymphocyte phenotyping, with estimates of percentages of T cells,
Influence of alcohol consumption on immunological status: a review
European Journal of Clinical Nutrition, 2002
The aim of this review is to present and discuss the effect of different levels of alcohol consumption on the immune system. Not only the amount consumed but also the type of alcoholic beverage have to be taken into account in order to determine the consequences on activity, number, distribution, balance, interaction and response of immunocompetent cells. The association between alcohol exposure and the risk of developing an alcohol-related disease is multifactorial. In fact, age, gender, smoking habits, dietary intake and exercise are involved among other factors. The evaluation of the host cellular and humoral immune responses has shown that alcohol may induce some benefits when consumption is moderate. Moreover, those alcoholic beverages that contain antioxidants, such as red wine, could be protectors against immune cell damage. According to the literature consulted, the daily consumption of 10 -12 g and 20 -24 g of alcohol for women and men, respectively, is considered to be a moderate intake; the type of beverage has been established not to be important when defining moderation. Particular attention is often focused on the U-or J-shaped curve which also suggests that light to moderate drinking produces a protective effect. Such an inverse relationship indicates a reduction of risk for both light and moderate consumers and a higher risk not only for hard drinkers, but also for non-consumers.
Dose-dependent effects of chronic alcohol drinking on peripheral immune responses
Scientific Reports
It is well established that chronic heavy alcohol drinking (CHD) results in significant organ damage, increased susceptibility to infections, and poor outcomes following injury. In contrast, chronic moderate drinking (CMD) has been associated with improved cardiovascular health and immunity. These differential outcomes have been linked to alterations in both innate and adaptive branches of the immune system; however, the mechanisms remain poorly understood. To address this question, we determined the impact of chronic drinking on the transcriptional and functional responses of peripheral blood mononuclear cells (PBMC) collected from male rhesus macaques classified as CMD or CHD after 12 months of voluntary ethanol self-administration. Our analysis suggests that chronic alcohol drinking, regardless of dose alters resting transcriptomes of PBMC, with the largest impact seen in innate immune cells. These transcriptional changes are partially explained by alterations in microRNA profiles. Additionally, chronic alcohol drinking is associated with a dose dependent heightened inflammatory profiled at resting and following LPS stimulation. Moreover, we observed a dose-dependent shift in the kinetics of transcriptional responses to LPS. These findings may explain the dichotomy in clinical and immunological outcomes observed with moderate versus heavy alcohol drinking. Observational studies in humans have reported strong associations between chronic heavy drinking (CHD) and significant organ damage as indicated by increased incidence of acute respiratory stress syndrome (ARDS) 1 , alcoholic liver disease (ALD) 2 , certain cancers 3-5 , cardiovascular diseases 6,7 , and sepsis 8. Moreover, CHD results in increased susceptibility to pneumonia 9,10 , tuberculosis 11-13 , and faster progression of hepatitis C virus (HCV) 14 and HIV infections 15. Furthermore, individuals who engage in CHD exhibit higher rates of postoperative complications 16 , slower recovery from infection and trauma 16 , poor vaccine responses 17 , and wound healing 18. In contrast, chronic moderate drinking (CMD) has been associated with decreased cardiovascular disease, improved insulin sensitivity, and decreased incidence of the common cold in humans 19-21. These studies suggest that chronic moderate and heavy drinking exert opposing effects on the human immune system; however, the mechanisms by which chronic drinking modulates immunity remain poorly understood. The earliest studies on CHD suggested that long-term drinking (several years to decades) is associated with reduction in T-cell numbers 22 , loss of naïve T-cells 22,23 , increased CD8+ T-cell activation and proliferation 24 , and increased serum immunoglobulin levels 25. CHD also results in higher levels of circulating pro-inflammatory mediators TNFα, IL-1β, and IL-6 26. Interpretation of these clinical studies are however confounded by age, erratic drinking patterns, sex, smoking status, use of recreational or illicit drugs, and nutritional deficiencies. More recent in vitro studies where peripheral blood mononuclear cells (PBMC) isolated from healthy humans (not meeting the criteria of CHD) or monocytic cell lines were cultured with ethanol suggest that short (hours) and long-term (days) exposure have opposing effects on inflammatory responses of innate immune cells 27. Specifically, while short-term exposure increased production of regulatory cytokines (e.g. IL-10) and decreased production of pro-inflammatory factors (TNFα and IL-6) 28-30 , long-term exposure heightened TNFα secretion following stimulation with toll-like receptor (TLR) 4 and 8 ligands 29,31,32. However, these in vitro studies do not take into account the effects of ethanol's metabolites and the pleiotropic impact of ethanol consumption on other immune cells, which can be modeled only using in vivo exposure.
Alcoholism: Clinical and Experimental Research, 1999
To analyze adhesion molecule expression on peripheral blood mononuclear cells (PBMCs) and on different lymphocyte subpopulations (CD2+, CDW, CD19+, and CD56+ subsets) in chronic alcoholism, 30 well-nourished chronic alcoholics without ethanol-related diseases and 30 matched controls were included in the study. Adhesion molecules that mediate adhesion to other cells and to extracellular matrix proteins, and whose cellular expression is modtied during lymphocyte activation, were selected for study. Adetailed clinical evaluation, laboratory analysis, nutritional assessment, and study of adhesion molecule expression was performed. A significant higher expression of CD29 (p,-integrin) (p = 0.001), VIA-3 ( p = 0.002),
Expansions of CD8CD28- and CD8TcRVbeta5.2 T Cells in Peripheral Blood of Heavy Alcohol Drinkers
Alcoholism-clinical and Experimental Research, 2000
Background: Despite heavy alcohol consumption, only a low percentage of heavy drinkers develop liver disease. Imbalances in T-cell subsets and iron metabolism parameters are common findings in heavy drinkers, yet the possible role played by discrete T-lymphocyte subsets under heavy alcohol consumption remains unclear.Methods: To gain new insights into the possible role played by T lymphocytes during alcohol consumption, characterization of CD28 expression and TcR repertoire in peripheral blood CD4+ and CD8+ T cells by two and three-color flow cytometry was performed. A group of heavy alcohol drinkers (AHD, n= 71) and a group of age-matched controls (n= 81), both HLA-phenotyped and HFE-genotyped, constituted the groups under study.Results: Marked expansions of CD28− T cells within the CD8+ but not the CD4+ T-cell pool were observed in AHD compared with controls. These CD8+CD28− expansions were paralleled by expansions of CD8+ T cells bearing specific TcR Vα/β chains, namely Vβ5.2. Moreover, AHD, but not controls, carrying the H63D mutation in the HFE gene showed significantly higher percentages of CD28− T cells within the CD8+ T-cell pool than AHD carrying the normal HFE gene. Finally, high numbers of CD8+CD28− T cells in AHD were associated with lower levels of the liver-related enzymes ALT and GGT.Conclusions: This study showed that under active ethanol consumption, expansions of discrete CD8+ T-cell subsets occur within the CD8+ T-cell pool, that molecules of the MHC-class I locus seem to influence the extent of the expansions, and that high numbers of CD8+CD28− T cells are associated with low levels of liver enzymes in AHD.
Alcoholism: Clinical and Experimental Research, 1999
BACKGROUND: In the present study, we analyzed, at the intracellular level, the pattern of cytokine secretion by the major CD4+ and CD8strong+ peripheral blood (PB) T-cell subsets in patients with chronic alcoholism, and we correlated it both with the ethanol (EtOH) intake status and with the presence or not of alcoholic liver disease. METHODS: For that purpose, a total of 30 chronic alcoholic patients, 10 without liver disease (AWLD group) and 20 diagnosed with alcoholic liver cirrhosis (ALC) were studied. In all cases, flow cytometric measurement of intracellular expression of interferon-gamma (IFN-gamma), interleukin (IL)-2, and IL-4 was performed on PB CD4+ and CD8strong+ T lymphocytes. RESULTS: After studying AWLD patients, we found increased numbers of both CD4+ and CD8strong+ PB T cells with detectable cytoplasmic levels of the IL-2 and IFN-gamma T helper (Th)-1-associated cytokines, the greater increase being observed for this latter cytokine (p<0.001 for CD4+ and p<0.01 for CD8strong+ T cells). Regarding ALC patients, the pattern of expression of intracellular cytokines by PB T cells was different depending on the status of EtOH intake at the moment of entering this study. Accordingly, as in AWLD patients, ALC individuals who were actively drinking also displayed increased numbers of both CD4+ and CD8strong+ T cells expressing Th-1-associated cytokines. However, in these patients, expression of IFN-gamma, although being significantly greater than that observed in control individuals (p<0.05), was significantly lower than that in AWLD patients (p<0.01 and p<0.05, for CD4+ and CD8strong+ T cells, respectively). After a withdrawal period of > or =1 yr, ALC patients did not show significant changes in the cytoplasmic expression of Th-1-associated cytokines compared with the control group; in contrast, these patients showed a marked increase on the proportion of CD4+ and CD8strong+ T cells expressing IL-4, a Th-2-associated cytokine (p<0.01). After considering the ratio between the number of T cells expressing Th- (IFN-gamma)- and Th-2 (IL-4)-associated cytokines in each individual, we found that there was a significant imbalance in this ratio, with a predominance of IFN-gamma-producing T cells over IL-4+ T lymphocytes during EtOH intake. CONCLUSIONS: Our results showed that in patients with chronic alcoholism, active EtOH intake is associated with a Th-1 pattern of cytokine production by PB T cells.
Effects of ethanol administration on parameters of immunocompetency in rats
Journal of leukocyte biology, 1986
Ethanol administered to rats intragastrically in doses sufficient to cause dependency resulted in a rapid cell loss from the thymus and spleen. Cell loss from the peripheral blood was due primarily to a loss of lymphocytes, but a concomitant granulocytosis resulted in only small changes in the total leukocyte count. Lymphocyte proliferation to both T- and B-cell mitogens was severely compromised by ethanol treatment. The cell loss and functional lymphocyte impairment also occurred at half the ethanol dose required to induce dependency. Although cell numbers recovered relatively quickly after ethanol withdrawal, lymphocyte function, as measured by proliferation, recovered more slowly. Ethanol administration before or during immunization with sheep erythrocytes resulted in an impairment in the ability of animals to respond with a primary immune response to this antigen. These data suggest that ethanol given in quantities sufficient to produce dependence impairs in vitro and in vivo pa...
Alcoholism: Clinical and Experimental Research, 1994
Modification of the mucosa-associated intestinal immune system of female C57BL/6 mice was studied during consumption of the Lieber-DeCarli diet supplemented with 5% v/v ethanol or laboratory chow with ethanol (20% w/v) in the drinking water. All groups received ethanol for 11 weeks. Mice fed the Lieber-DeCarli diet had fewer CD8+ cells/villus than the chow-fed controls. Mice that received ethanol in the drinking water had fewer IgA-containing cells and CD8+ cells than controls. There were no differences in the number of cells in the mesenteric lymph nodes between ethanol-treated mice and their respective controls. Nevertheless, chow-fed control mice had more cells than those fed the Lieber-DeCarli control diet. Although no differences were detected in the percentages of CD4+, CD8+, LECAM-1+, and LECAM-1+ CD4+ cells, there was a decrease in the percentage of LECAM-1+ CD8+ cells in ethanol-fed mice when compared with their Lieber-DeCarli controls. Mice receiving ethanol in the drinking water showed alterations in the CD4 CD45RC subsets and in the CD8 CD45RC subsets. Similar results were observed in mice receiving Lieber-DeCarli diets alone or supplemented with ethanol. The low dose, chronic exposure of dietary ethanol in the Lieber-DeCarli-fed mice did not significantly affect the numbers of various thymocyte subsets. But, a decrease in the percentage of CD4-CD8+ cells was observed in the thymus of mice receiving ethanol in the drinking water. Chronic ethanol consumption caused significant decreases in the number of CD8+ and IgA+ cells in the intestinal lamina propria, important in mucosal immune defenses.