M. Yeh et al., EFFECTS OF EXOGENOUS CYTOKINES ON THE ETHANOL-MEDIATED SUPPRESSION OFMURINE THYMOCYTE PROLIFERATION, International journal of immunopharmacology, 18(3), 1996, pp. 219-226
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.