INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA AND PROSTAGLANDIN-E2 PRODUCTION BY ETHANOL IN HUMAN MONOCYTES

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 (TGFbeta) and prostaglandin 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 TGFbeta (P < 0.045 and P < 0.001, respectively). Furthermore, MO pretreatment with both 50 and 150 mm ethanol augmented TGFbeta 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 TGFbeta production in interferon gamma (IFN-gamma)-activated MO in response to MDP stimulus (P < 0.05). MO TGFbeta levels, however, were always lower in IFN-gamma-activated than in non-IFN-gamma-activated MO after the same stimulation with ethanol plus MDP, suggesting that MO preactivation by IFN-gamma can partially counteract the TGFbeta inducing potential of ethanol. Similar to its TGFbeta-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. TGFbeta induction by ethanol was unaffected by the presence of cyclooxygenase inhibitor, suggesting that ethanol-induced MO TGFbeta production does not require MO PGE2 production. These results indicate that ethanol is a potent inducer for inhibitory MO mediators, TGFbeta and PGE2, and also has the capacity to augment MO TGFbeta production in response to subsequent stimulation. Thus, ethanol-induced elevation of MO TGFbeta and PGE2 production might contribute to decreased T cell proliferation and abnormal MO functions after alcohol exposure, resulting in a depressed immune response.