EFFECTS OF PRENATAL ALCOHOL AND PAIR FEEDING ON LIPOPOLYSACCHARIDE-INDUCED SECRETION OF TNF-ALPHA AND CORTICOSTERONE

Fetal alcohol exposure (FAE) produces profound alterations in immunolo gical and neuroendocrine functions. The present study examined the eff ects of FAE on the secretion of tumor necrosis factor (TNF-alpha) and corticosterone following administration of lipopolysaccharide (LPS) in normal (N) adult rats, in adult offspring of dams fed a liquid diet s upplemented with ethanol (E), and in pair-fed control offspring (P). L PS-induced TNF-alpha secretion was not affected by either gender or pr enatal treatment. In contrast, LPS-induced corticosterone secretion wa s significantly greater in female than in male rats, and at 60-min pos t-LPS was significantly higher in E and P, compared to N females. Ovar iectomy significantly inhibited LPS-induced TNF-alpha secretion in E, but not in P and N, rats and chronic replacement with 17-beta-estradio l markedly inhibited TNF-alpha secretion in ovariectomized E and N, bu t not in P, rats. In contrast, ovariectomy reduced the effects of LPS on corticosterone secretion in all groups, and chronic replacement wit h 17-beta-estradiol reversed this effect. These findings indicate that LPS-induced secretion of corticosterone, but not TNF-alpha, is affect ed by prenatal manipulations and by gender. In addition, alterations i n the hormonal environment in females modulate LPS-induced corticoster one secretion in all prenatal treatment groups, but differentially inf luence TNF-alpha secretion in rats exposed to alcohol, restricted feed ing, or normal diets in utero. (C) 1998 Elsevier Science Inc.