Human monocyte IL-10 production is increased by acute ethanol treatment.
Immune alterations after acute ethanol treatment are characterized by abnormal monocyte mediator production and antigen presentation capacity. Here, we tested the hypothesis that some of the regulatory effects of ethanol on monocyte functions are mediated by elevated M phi IL-10 production. Physiologically relevant in vitro doses of ethanol (25-100 mM) resulted in significantly increased IL-10 secretion by normal blood monocytes after 18 h stimulation. We found that monocyte IL-10 production induced by either ethanol or LPS increased at 10 h, maximized at 18 h and decreased by 40 h post-stimulation. Furthermore, ethanol significantly augmented LPS-induced monocyte IL-10 secretion at 18 h. Data also show that ethanol-induced changes in monocyte IL-10 mRNA levels mirror those seen at the protein levels. Greater IL-10 levels and IL-10 induction by LPS in adherent compared to non-adherent M phi imply that adherence is an important co-stimulator for IL-10 production in human M phi. We further showed that cyclooxygenase inhibitor treatment augments M phi IL-10 production suggesting that elevated PGE2 (and cAMP) is not necessary for IL-10 induction by ethanol or LPS in isolated M phi. Finally, our data demonstrate that ethanol-induced elevated M phi IL-10 contributes to the decreased M phi TNF-alpha production seen after acute ethanol treatment. However, observation of an ethanol-induced decrease in TNF-alpha mRNA as early as 1.5 h after stimulation indicate that ethanol has an additional, IL-10 independent, effect on M phi TNF-alpha production. These results suggest that elevated monocyte-derived IL-10 can contribute to the monocyte as well as other immune abnormalities after acute ethanol uptake.
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
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P
Mandrekar
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D
Catalano
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L
Girouard
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G
Szabo
D000435:Alcoholic Intoxication / Q000097:blood*; D002448:Cell Adhesion; D000242:Cyclic AMP / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000431:Ethanol; D000242:Cyclic AMP