IMMUNOSUPPRESSION IN ADULT FEMALE B6C3F1 MICE BY CHRONIC EXPOSURE TO ETHANOL IN A LIQUID DIET

The overall objective of these studies was to characterize the effects of ethanol on the immunocompetence of adult female B6C3F1 mice. To ob tain a significant suppression in the antibody response to SRBC, splen ocytes from untreated mice had to be directly exposed to concentration s of ethanol from 0.3% to 3.0%, or to acetaldehyde at concentrations g reater than 0.03%. We do not believe that these results are consistent with a role by a direct effect by either ethanol or its primary metab olite because these concentrations are higher than what could be obtai ned as reasonable blood levels. For in vivo exposure, we employed a pa ir-feeding regimen which was based on a liquid diet containing 5% etha nol (v/v) that provided 36% of the caloric intake as ethanol. Our resu lts indicated that there was a definite temporal relationship to the c onsequent suppression of the antibody response to SRBC in that no effe ct was observed after 14 days exposure, and that the magnitude of the suppression increased from 18% after 21 days to 70% after 42 days. We also monitored the liver for histopathology and observed that the etha nol-induced liver damage was restricted to steatosis (fatty liver), wh ich was also manifested with time and which was most pronounced after 42 days exposure. In contrast to our results with the in vivo antibody response, we saw no effect on mitogen-induced proliferation by spleno cytes from ethanol-treated mice. These results prompted us to measure in vitro antibody responses by splenocytes from ethanol-treated mice. We saw no suppression of the in vitro antibody responses to SRBC, DNP- Ficoll or LPS after any length of exposure to ethanol, and speculated that the basis for the suppression of the in vivo antibody response wa s an indirect consequence of exposure. We subsequently determined that when normal splenocytes were cultured in 5% serum from ethanol-expose d mice (42-day group), there was a >80% suppression relative to the se rum from the pair-fed controls. As important controls for these studie s, we have demonstrated that there was no difference between the respo nses of normal lymphocytes cultured in 5% normal mouse serum and in 5% serum taken from the pair-fed restricted controls. A determination of the ethanol content in the serum from ethanol-exposed mice (42-day gr oup) indicated that the amount of ethanol present in these cultures wa s <0.003%. These results suggest that the mechanism of ethanol-induced immunosuppression is at least in part due to an indirect consequence of chronic exposure, which is possibly mediated by a serum factor.