Chronic Alcoholism Is Associated With an Imbalanced Production of Th‐1/Th‐2 Cytokines by Peripheral Blood T Cells

Laso, Francisco‐Javier; Iglesias‐Osma, C.; Ciudad, Juana; López, Antonio; Pastor, Isabel; Órfão, Alberto

doi:10.1111/j.1530-0277.1999.tb04351.x

Cited by 76 publications

(45 citation statements)

References 33 publications

(22 reference statements)

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“…Lifestyle factors such as physical activity, smoking and alcohol intake are known to influence the percentage of peripheral blood lymphocytes [3,9,10,13]. In our series, individuals who performed health-enhancing physical activity had a higher percentage of lymphocytes and DN cells and a lower percentage of CD4+ cells than minimally active or inactive individuals.…”

Section: Discussionmentioning

confidence: 52%

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Influence of Age, Gender and Lifestyle in Lymphocyte Subsets: Report from the Spanish Gait-2 Study

et al. 2012

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Introduction: Flow cytometry analysis of lymphocyte subsets in peripheral blood is a common technique in diagnostic laboratories. Abnormal values have been identified in prevalent infections, autoimmune disorders and neoplastic diseases. Reference ranges for lymphocyte subsets of a healthy population from Spain are scarce. Methods: The study was performed on 319 healthy subjects, aged 4–88 years, from 709 individuals enrolled in the GAIT-2 Project (Genetic Analysis of Idiopathic Thrombophilia). Health status, age, sex, fertility, BMI and lifestyle (physical activity, cigarette smoking and ethanol intake) were assessed using standardized criteria. The percentage of lymphocyte subsets was determined using flow cytometry (Lymphogram™). Percentages of CD3+, CD4+, CD8+, CD19+, CD3–CD56+, CD3+CD4–CD8– double-negative (DN) T cells, CD3+CD4+CD8+ double-positive T cells and the CD4+/CD8+ ratio were recorded for each case. Results: Children had a significantly higher percentage of CD19+ and DN cells than adults. Women had a significantly higher percentage of CD3+ and CD4+ and a lower percentage of natural killer cells than men. Increases in BMI were inversely associated with the percentage of DN cells. Physical activity increased the percentage of lymphocytes and DN cells. Alcohol consumers had a lower percentage of CD19+ and DN cells, and a higher percentage of CD4+. Conclusion: This study provides reference ranges for lymphocyte subsets of healthy children and adults in a Mediterranean population (Spain) and determines the influence of lifestyle factors on these values.

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Section: Discussionmentioning

confidence: 52%

“…Other determinants related to lifestyle can also affect lymphocyte subsets. These include physical activity [9], ethanol intake [10,11] and cigarette smoking [12]. The determination of lymphocyte subsets is also influenced by variations in the study design and analytical techniques and procedures [13].…”

Section: Introductionmentioning

confidence: 99%

Influence of Age, Gender and Lifestyle in Lymphocyte Subsets: Report from the Spanish Gait-2 Study

et al. 2012

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“…13,19 These results suggest similar IL-6 responses to liver injury in alcoholic liver disease and obesity-related liver disease in both humans and mice. [9][10][11][12][13] The consequences of chronic IL-6 over-expression and persistent signaling in alcoholic and obesity-related hepatocyte dysfunction are unknown, and the existing data are conflicting. Although administration of IL-6 improved the regenerative response in obese Zucker rats, hyperstimulation with IL-6 administered to transgenic mice expressing soluble human IL-6R␣ actually repressed cell cycle progression after hepatectomy, suggesting that IL-6 can inhibit liver growth after injury.…”

mentioning

confidence: 99%

“…These reports suggest an important role of IL-6 in acute liver injury and a beneficial effect of IL-6 production in repetitive liver injury. [9][10][11][12][13] IL-6 is both pro-mitogenic and anti-apoptotic for hepatocytes. We have demonstrated that prolonged exposure to continuous, supraphysiological levels of IL-6 induces hepatocyte proliferation in vivo.…”

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confidence: 99%

Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair

et al. 2006

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Interleukin-6 (IL-6) is an important mediator of liver regeneration and repair that is also elevated in chronic liver diseases, including fatty liver of obesity and cirrhosis. IL-6 has been reported both to delay and accelerate liver regeneration. We examined the effects on liver injury and regeneration of a continuous administration of exogenous IL-6 to mice by injection of an IL-6 -expressing CHO-cell line in athymic nude mice and by osmotic mini-pump delivery of recombinant murine IL-6. Short-term IL-6 administration (1-2 days) accelerated early recovery of liver mass, whereas more long-term administration (5-7 days) markedly impaired liver regeneration. Similarly, short-term IL-6 treatment increased hepatic resistance to the lethal effects of the Fas agonist Jo-2, but on more prolonged IL-6 exposure the Jo-2 resistance vanished. IL-6 administration initially induced expression of the anti-apoptotic proteins Bcl-2 and Bcl-x L , correlating with protection against Fas-mediated cell death. More prolonged IL-6 administration, however, resulted in marked induction of the proapoptotic protein Bax. This result coincided with increased activation of the type II or intrinsic, mitochondrial path to cell death, manifested by increased caspase-9 activation and increased cytochrome c release after Jo-2 exposure. These data demonstrate that IL-6 can function acutely to improve hepatic regeneration and repair, but that more chronic exposure not only abolishes the protective effects of IL-6, but actually sensitizes the liver to injury and death. In conclusion, elevated IL-6 in certain chronic liver diseases contributes to an increased likelihood of liver failure after injury. (HEPATOLOGY 2006;43:474-484.)

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“…response were associated with immune abnormalities (10)(11)(12)(13). Chronic alcoholism is associated also with numerical, phenotypical, and functional changes in circulating peripheral blood dendritic cells (DCs).…”

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confidence: 99%

Chronic and Acute Alcohol Exposure Prevents Monocyte-Derived Dendritic Cells from Differentiating and Maturing

Buttari

Profumo

Mancinelli

et al. 2008

Int J Immunopathol Pharmacol

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Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytoftuorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (aleiDCs). Alc-iDCs showed fewer Clrla" cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-a and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naive allogeneic T cells into Thl cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.Emerging evidence shows an increased incidence of infectious diseases, as well as a greater susceptibility to cancer in humans chronically abusing alcohol (1-5). Evidence from human and animal studies in vivo, as well as from in vitro experiments suggests that alcohol abuse may exert adverse immunomodulatory effects on innate and adaptive immune responses (4, 6-9). Alcoholinduced immune dysfunctions depend on various factors including the dose and duration of alcohol exposure (chronic vs acute) and on the presence and characteristics of additional stimuli such as microbial molecules.In chronic alcoholics and in a chronic ethanolfeeding model in mice, impaired antigen-specific T cell proliferation and a delayed-type hypersensitivity

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Chronic Alcoholism Is Associated With an Imbalanced Production of Th‐1/Th‐2 Cytokines by Peripheral Blood T Cells

Abstract: 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.

Cited by 76 publications

References 33 publications

Influence of Age, Gender and Lifestyle in Lymphocyte Subsets: Report from the Spanish Gait-2 Study

Influence of Age, Gender and Lifestyle in Lymphocyte Subsets: Report from the Spanish Gait-2 Study

Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair

Chronic and Acute Alcohol Exposure Prevents Monocyte-Derived Dendritic Cells from Differentiating and Maturing

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