REGULATION OF HUMAN MONOCYTE FUNCTIONS BY ACUTE ETHANOL TREATMENT - DECREASED TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-1-BETA AND ELEVATED INTERLEUKIN-10, AND TRANSFORMING GROWTH-FACTOR-BETA PRODUCTION

We and others have previously shown that even acute ethanol exposure h as the capacity to modulate immune functions, particularly monocyte fu nctions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine productio n in human blood monocytes that, in turn, could contribute to the over all immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant do se of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterot oxin B (SEB), 1 mu g/ml of SEB] or Gram-negative [lipopolysaccharide ( LPS), 1 mu g/ml of LPS] origin both at the protein and mRNA levels. In contrast, acute ethanol treatment induces monocyte production of medi ators with immunoinhibitory potential, including transforming growth f actor-beta and IL-10. We further show that ethanol not only induces mo nocyte/macrophage (MO) IL-10 and transforming growth factor-beta, but even augments bacterial (both LPS and SEB) stimulation-induced product ion of both of these cytokines. IL-10 is a potent inhibitor of MO TNF alpha production. We found that ethanol-induced elevation in MO IL-10 levels contributes to the decreased MO TNF alpha production to bacteri al challenge in ethanol-exposed MO. However, mRNA levels for TNF alpha are downregulated as early as 1.5 hr after ethanol treatment, suggest ing that ethanol likely has an IL-10 independent, direct effect on ear ly signaling events of TNF alpha induction.