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

Abstract To test our hypothesis that monocytes (MØ) 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 (TGFβ) and prostaglandin E2 (PGE2) by human peripheral blood MØ. 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 TGFβ (P < 0.045 and β < 0.001, respectively). Furthermore, MØ pretreatment with both 50 and 150 mM ethanol augmented TGFjS production in response to subsequent stimulation with the synthetic bacterial analog, muramyl dipeptide (MDP) (P < 0.05 and β < 0.001, respectively). Ethanol also increased TGFØ production in interferon β (IFNβ)‐ activated MØ in response to MDP stimulus (P < 0.05). MØ TGFβ levels, however, were always lower in IFNβ‐ activated than in non‐IFNβ‐activated MØ after the same stimulation with ethanol plus MDP, suggesting that MØ preactivation by IFN7 can partially counteract the TGFβ inducing potential of ethanol. Similar to its TGFβ ‐ inducing potential, ethanol (150 mM) had the capacity to induce PGE2 production in adherent human MØ (P < 0.045). However, ethanol failed to augment MØ PGE2 production induced by the PGE2 secretagogue, MDP. TGFjS induction by ethanol was unaffected by the presence of cyclooxygenase inhibitor, suggesting that ethanol‐induced MØ TGFß production does not require MØ PG£2 production. These results indicate that ethanol is a potent inducer for inhibitory MØ mediators, TGFjS and PGE2, and also has the capacity to augment MØ TGFß production in response to subsequent stimulation. Thus, ethanol‐induced elevation of MØ TGFß and PGE2 production might contribute to decreased β cell proliferation and abnormal MØ functions after alcohol exposure, resulting in a depressed immune response.