REGULATION OF MONOCYTE INTERLEUKIN-12 PRODUCTION BY ACUTE ALCOHOL - AROLE FOR INHIBITION BY INTERLEUKIN-10

Acute ethanol treatment results in decreased antigen presentation capa city (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 ( IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL -10, respectively. Thus, we tested the hypothesis that acute alcohol t reatment might affect Th1/Th2 immune balance by altering monocyte prod uction of IL-12 and IL-10. Neither acute ethanol treatment atone (25 t o 100 mM) nor its combination with a bacterial challenge Staphylococca l enterotoxin B (SEE) induced IL-12 production in isolated blood monoc ytes. In contrast, the same physiological alcohol concentrations incre ased monocyte IL-10 revels, suggesting that ethanol can induce a dysba lance of monocyte-derived mediator production at the expense of Th1 cy tokines. However, we found that monocyte activation with interferon-ga mma (IFN-gamma) can prevent the preferential IL-10 induction by ethano l. IFN-gamma (100 units/ml) inhibited monocyte IL-10 production whethe r induced by 1 mu g/ml of lipopolysaccharide (p < 0.01), 1 mu g/ml of SEE (p < 0.02), or a combination of bacterial stimulation + ethanol (l ipopolysaccharide: p < 0.01). Furthermore, decreased IL-10 was concomi tant to an increase in IL-12 production in IFN-gamma-treated monocytes . Moreover, acute ethanol treatment augmented IL-12 production in IFN- gamma-treated monocytes in response to SEE stimulation (25 mM ethanol, p < 0.01; 100 mM ethanol, p < 0.01). Experiments with anti-IL-10 neut ralizing antibody show that ethanol may prevent monocyte IL-12 inducti on via IL-10. These results suggest that inhibition of ethanol-induced IL-10 production by IFN-gamma treatment is permissive for IL-12 induc tion by alcohol stimulation in monocytes. Thus, our results imply that the presence or absence of IFN-gamma is critical in determining the e ffect of acute ethanol treatment on monocyte IL-12 versus IL-10 induct ion.