Szabo G, Verma B K, Fogarasi M, Catalano D E
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
J Leukoc Biol. 1992 Dec;52(6):602-10. doi: 10.1002/jlb.52.6.602.
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.
为了验证我们的假设，即单核细胞（M phi）及其介质是乙醇相关免疫抑制的主要促成因素，我们评估了急性乙醇处理对人外周血M phi产生转化生长因子-β（TGF beta）和前列腺素E2（PGE2）的调节能力。我们证明，用50或150 mM乙醇对贴壁M phi进行急性体外处理可导致TGF beta产生显著增加（分别为P < 0.045和P < 0.001）。此外，用50和150 mM乙醇对M phi进行预处理可增强其对随后合成细菌类似物胞壁酰二肽（MDP）刺激的TGF beta产生（分别为P < 0.05和P < 0.001）。乙醇还可增加干扰素γ（IFN gamma）激活的M phi在MDP刺激下的TGF beta产生（P < 0.05）。然而，在用乙醇加MDP进行相同刺激后，IFN gamma激活的M phi中的TGF beta水平总是低于未被IFN gamma激活的M phi，这表明IFN gamma对M phi的预激活可部分抵消乙醇诱导TGF beta的潜力。与其诱导TGF beta的潜力相似，乙醇（150 mM）能够诱导贴壁人M phi产生PGE2（P < 0.045）。然而，乙醇未能增强由PGE2促分泌剂MDP诱导的M phi PGE2产生。乙醇诱导的TGF beta不受环氧化酶抑制剂存在的影响，这表明乙醇诱导的M phi TGF beta产生不需要M phi产生PGE2。这些结果表明，乙醇是抑制性M phi介质TGF beta和PGE2的有效诱导剂，并且还具有增强M phi对随后刺激的TGF beta产生的能力。因此，乙醇诱导的M phi TGF beta和PGE2产生增加可能导致酒精暴露后T细胞增殖减少和M phi功能异常，从而导致免疫反应受到抑制。
