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.
D000911:Antibodies, Monoclonal / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D000431:Ethanol; D013755:Tetradecanoylphorbol Acetate