FETAL ALCOHOL EXPOSURE AUGMENTS THE BLUNTING OF TUMOR-NECROSIS-FACTORPRODUCTION IN-VITRO RESULTING FROM IN-VIVO PRIMING WITH LIPOPOLYSACCHARIDE IN YOUNG-ADULT MALE BUT NOT FEMALE RATS

We previously reported altered responses of thymocytes and splenocytes to mitogen stimulation in fetal alcohol-exposed (FAE) male Sprague-Da wley rats. We also reported enhanced neuroendocrine responses to stres sful stimuli in these animals. The experiments we describe herein aime d at testing whether young adult FAE rats manifest a notable dysregula tion in the neuroendocrine-immune response to pathogen administration. We tested the effect of in vivo priming of the animal with a low dose of endotoxin [lipopolysaccharide (LPS), 5 mu g/kg], considered to be suboptimal from the perspective of mounting detectable levels of circu lating monokines several hours after administration, upon the producti on of immunoreactive tumor necrosis factor (TNF-alpha) in response to a further in vitro challenge of peripheral blood mononuclear cells wit h 2.5 mu g/ml of LPS 90 min after priming. We show that the response t o the LPS pathogen in vitro after priming is significantly blunted (p < 0.01) in male rats exposed prenatally to alcohol, compared with cont rol male animals. FAE female rats and FAE ovariectomized female rats d o not show significant differences in the priming response, compared w ith control animals. We also show that there is no correspondence betw een plasma corticosterone levels and TNF-alpha production after primin g in any of the groups tested.