Induction of transforming growth factor-beta and prostaglandin E2 production by ethanol in human monocytes.
To test our hypothesis that monocytes (M phi) and their mediators are major contributors to ethanol-related immunodepression, the modulating capacity of acute ethanol treatment was assessed on the production of transforming growth factor-beta (TGF beta) and prostaglandin E2 (PGE2) by human peripheral blood M phi. We demonstrate that acute in vitro treatment of adherent M phi with either 50 or 150 mM ethanol induced a significant increase in the production of TGF beta (P < 0.045 and P < 0.001, respectively). Furthermore, M phi pretreatment with both 50 and 150 mM ethanol augmented TGF beta production in response to subsequent stimulation with the synthetic bacterial analog, muramyl dipeptide (MDP) (P < 0.05 and P < 0.001, respectively). Ethanol also increased TGF beta production in interferon gamma (IFN gamma-activated M phi in response to MDP stimulus (P < 0.05). M phi TGF beta levels, however, were always lower in IFN gamma-activated than in non-IFN gamma-activated M phi after the same stimulation with ethanol plus MDP, suggesting that M phi preactivation by IFN gamma can partially counteract the TGF beta inducing potential of ethanol. Similar to its TGF beta-inducing potential, ethanol (150 mM) had the capacity to induce PGE2 production in adherent human M phi (P < 0.045). However, ethanol failed to augment M phi PGE2 production induced by the PGE2 secretagogue, MDP. TGF beta induction by ethanol was unaffected by the presence of cyclooxygenase inhibitor, suggesting that ethanol-induced M phi TGF beta production does not require M phi PGE2 production. These results indicate that ethanol is a potent inducer for inhibitory M phi mediators, TGF beta and PGE2, and also has the capacity to augment M phi TGF beta production in response to subsequent stimulation. Thus, ethanol-induced elevation of M phi TGF beta and PGE2 production might contribute to decreased T cell proliferation and abnormal M phi functions after alcohol exposure, resulting in a depressed immune response.
Szabo
G
G
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Verma
B K
BK
Fogarasi
M
M
Catalano
D E
DE
D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood*
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000431:Ethanol; D007371:Interferon-gamma; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin