Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and transforming growth factor-beta production.
We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 microgram/ml of SEB] or Gram-negative [lipopolysaccharide (LPS), 1 microgram/ml of LPS] origin both at the protein and mRNA levels. In contrast, acute ethanol treatment induces monocyte production of mediators with immunoinhibitory potential, including transforming growth factor-beta and IL-10. We further show that ethanol not only induces monocyte/macrophage (Mø) IL-10 and transforming growth factor-beta, but even augments bacterial (both LPS and SEB) stimulation-induced production of both of these cytokines. IL-10 is a potent inhibitor of Mø TNF alpha production. We found that ethanol-induced elevation in Mø IL-10 levels contributes to the decreased Mø TNF alpha production to bacterial challenge in ethanol-exposed Mø. However, mRNA levels for TNF alpha are downregulated as early as 1.5 hr after ethanol treatment, suggesting that ethanol likely has an IL-10 independent, direct effect on early signaling events of TNF alpha induction.
Szabo
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Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
Mandrekar
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Girouard
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Catalano
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D
D000328:Adult; D000435:Alcoholic Intoxication / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000276:immunology; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000431:Ethanol