Effects of exogenous cytokines on the ethanol-mediated suppression of murine thymocyte proliferation

Although attempts have been made to assess the effect of ethanol on murine thymocyte proliferation, the mechanism which accounts for the immunosuppressive effect of ethanol on the thymocyte proliferation has not been elucidated. Thus, a mouse model was used to determine (1) whether there is a similarity in the effect of ethanol exposure in vitro and in vivo on the proliferative response of thymocytes to phytohemagglutinin (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 that the proliferative response of thymocytes from mice fed on an ethanol-containing diet was significantly inhibited (P < 0.05) compared to that 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 concentrations (25-100 mM) significantly suppressed the mitogenic response of thymocytes to PHA (P < 0.05) in a dose-dependent manner. Our data also revealed that (1) ethanol did not significantly suppress IL-1 secretion by adherent macrophages stimulated by LPS, and (2) the addition of exogenous IL-1 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 mediated by insufficient IL-1. Finally, we present novel evidence that addition of exogenous IL-2 completely restores the impaired proliferative response of thymocytes from ethanol-fed mice to control levels. In summary, our results demonstrate that ethanol inhibits thymocyte proliferation in response to PHA, and that the inhibition is not due to insufficient IL-1. We also report that addition of exogenous IL-2 is sufficient to restore full proliferative capacity to thymocytes from ethanol-fed mice.