Induction of transforming growth factor-beta and prostaglandin E2 production by ethanol in human monocytes
Department of Surgery; Department of Medicine, Division of Gastroenterology
Cell Line; Cell Survival; Cells, Cultured; Dinoprostone; Dose-Response Relationship, Drug; Ethanol; Humans; Indomethacin; Interferon-gamma, Recombinant; Kinetics; Lipopolysaccharides; Monocytes; Tetradecanoylphorbol Acetate; Time Factors; Transforming Growth Factor beta
Gastroenterology | Primary Care | Surgery
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.
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Citation: J Leukoc Biol. 1992 Dec;52(6):602-10.