Induction of transforming growth factor-beta and prostaglandin E2 production by ethanol in human monocytes

Abstract: To test our hypothesis that monocytes (MO) 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 (TGFI3) and prostaglan-din E2 (PGE2) by human peripheral blood MO. We demonstrate that acute in vitro treatment of adherent MO with either 50 or 150 mM ethanol induced a significant increase in the production of TGFf3 (P < 0.045 and P < 0.001, respectively). Furthermore, MO pretreat-ment with both 50 and 150 mM ethanol augmented TGF/3 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 TGF3 production in interferon ‘y (IFNy)-activated MO in response to MDP stimulus (P < 0.05). MO TGF/3 levels, however, were always lower in IFNy-activated than in non-IFN-y-activated MO after the same stimulation with ethanol plus MDP, suggesting that MO preactivation by IFNy can partially counteract the TGFf3 inducing potential of ethanol. Similar to its TGF/3-inducing potential, ethanol (150 mM) had the capacity to induce PGE2 production in adherent human MO (P < 0.045). However, ethanol failed to augment MO PGE2 production induced by the PGE2 secretagogue, MDP. TGFI3 induction by ethanol was unaffected by the presence of cyclooxygenase inhibitor, suggesting that ethanol-induced MO TGFI3 production does not require MO PGE2 production. These results indicate that ethanol is a potent inducer for inhibitory MO mediators, TGF/3 and PGE2, and also has the capacity to augment MO TGFI3 production in response to subsequent stimulation. Thus, ethanol-induced elevation of MO TGF/3 and PGE2 production might contribute to decreased T cell prolifera-tion and abnormal MO functions after alcohol exposure, resulting in a depressed immune response. J. Leukoc