REGULATION OF MONOCYTE IL-12 PRODUCTION - AUGMENTATION BY LYMPHOCYTE CONTACT AND ACUTE ETHANOL TREATMENT, INHIBITION BY ELEVATED INTRACELLULAR CAMP

IL-12, a monocyte-derived cytokine, is pivotal in activation of cellul ar immune response and inflammation. Both inflammatory response and ce llular immunity are impaired by acute ethanol consumption, Here, we fo und that in vitro acute ethanol treatment (25-100 mM) results in a dos e-dependent and significant increase of IL-12 in IFN-gamma (100 U/ml) plus Staphylococcal enterotoxin B (SEB; 1 mu g/ml) stimulated monocyte s and mononuclear cells but not in unstimulated cells from non-alcohol ic blood donors. There was significantly greater IL-12 production in t he MMC population compared to isolated M phi (P < 0.001). Prevention o f monocyte surface contact with either purified T lymphocytes or monoc yte-depleted MNC resulted in a significant, 65 +/- 20%, decrease in IL -12 production regardless of IFN-gamma, SEE or ethanol stimulation sug gesting that M phi T-cell surface contact provides an additional signa l for IL-12 production. In addition to cell surface contact, soluble m ediators, particularly IL-10 and PGE, may regulate IL-12 production. T he cyclooxygenase inhibitor, Indomethacin (10(-6)M), augmented both IL -12 and IL-10 levels in isolated monocytes and mononuclear cells wheth er induced by medium, SEB or SEB plus 25 mM ethanol suggesting that re gulation of IL-12-production via the cyclooxygenase pathway is indepen dent of IL-10. Finally, elevation of intracellular cAMP levels by dbcA MP treatment consistently inhibited IL-12 as well as IL-10 production in monocytes induced by IFN-gamma or IFN-gamma plus 25 mM ethanol. The se data suggest that augmentation of monocyte IL-12 by acute ethanol i s not mediated via the cAMP pathway. (C) 1998 International Society fo r Immunopharmacology. Published by Elsevier Science Ltd.