EFFECTS OF EXOGENOUS CYTOKINES ON THE ETHANOL-MEDIATED SUPPRESSION OFMURINE THYMOCYTE PROLIFERATION

Although attempts have been made to assess the effect of ethanol on mu rine thymocyte proliferation, the mechanism which accounts for the imm unosuppressive effect of ethanol on the thymocyte proliferation has no t been elucidated. Thus, a mouse model was used to determine (1) wheth er there is a similarity in the effect of ethanol exposure in vitro an d in vivo on the proliferative response of thymocytes to phytohemagglu tinin (PHA),(2) whether ethanol exposure affects the responsiveness of thymocytes to exogenous interleukin (IL)-1 and IL-2, and (3) whether ethanol affects IL-1 production by peritoneal macrophages. We found th at the proliferative response of thymocytes from mice fed on an ethano l-containing diet was significantly inhibited (P<0.05) compared to tha t in mice fed on maltose or standard diets. We also observed that low concentrations of ethanol (12.5 mM) appeared to enhance the mitogenic response of thymocytes to PHA, but the response was not significantly greater than that of controls (P>0.05). Ethanol at higher concentratio ns (25-100 mM) significantly suppressed the mitogenic response of thym ocytes to PHA (P<0.05) in a dose-dependent manner. Our data also revea led that (1) ethanol did not significantly suppress IL-l secretion by adherent macrophages stimulated by LPS, and (2) the addition of exogen ous IL-I was insufficient to restore full responsiveness in thymocytes from ethanol-fed mice. Taken together, these results suggest that the suppressive effect of ethanol on thymocyte proliferation is not media ted by insufficient IL-1. Finally, we present novel evidence that addi tion of exogenous IL 2 completely restores the impaired proliferative response of thymocytes from ethanol-fed mice to control levels. In sum mary, our results demonstrate that ethanol inhibits thymocyte prolifer ation in response to PHA, and that the inhibition is not due to insuff icient IL-1. We also report that addition of exogenous IL-2 is suffici ent to restore full proliferative capacity to thymocytes from ethanol- fed mice.