A novel mechanism of immunosuppression mediated by ethanol.

Ethanol in concentrations equivalent to levels achieved by the ingestion of moderate amounts of alcoholic beverages has been shown to inhibit human T-lymphocyte proliferation after activation in vitro by mitogens, phorbol myristic acetate, or anti-CD3 monoclonal antibodies. As determined by probit analysis, this inhibition was monophasic, suggesting that ethanol affected a single limiting component of T-cell proliferation. In experiments designed to test the effect of ethanol on various aspects of proliferation, it was demonstrated that ethanol did not inhibit interleukin 2 (IL-2) production or the acquisition of IL-2 receptors. However, the capacity of exogenously supplied IL-2 to stimulate proliferation of T cells that had previously acquired IL-2 receptors was suppressed by ethanol in a dose-dependent manner, and this suppression was monophasic. Consequently, ethanol was able to inhibit T-lymphocyte proliferation when added several days after the initial stimulation. This mechanism appears to be unique among immunosuppressive agents thus far studied; cyclosporin A and corticosteroids inhibit IL-2 production and are required at the initiation of activation for maximal effect. Synergistic inhibition of T-cell proliferation was seen with ethanol plus cyclosporin A: the level of inhibition with 250 ng/ml cyclosporin A alone was equivalent to the level seen with 62 ng/ml cyclosporin A plus 5 mM (24 mg%) ethanol.