Effects of fetal alcohol exposure on fever, sickness behavior, and pituitary-adrenal activation induced by interleukin-1 beta in young adult rats.

Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We have previously reported that fetal alcohol-exposed rats show markedly decreased lipopolysaccharide-induced fever and suggested that fetal alcohol exposure (FAE) impairs the communication between the immune and the nervous systems. The present study examined the effects of interleukin-1 beta (IL-1) on body temperature, motor activity, ingestive behavior, and pituitary-adrenal activation in fetal alcohol-exposed and control rats. Transmitters for continuous biotelemetric recording of body temperature and motor activity were implanted i.p. in normal (N) adult rats, offspring of dams fed a liquid diet supplemented with ethanol (E), and pair-fed control offspring (P). In one experiment, rats were injected with either IL-1 (2 micrograms/kg, i.p.) or saline at the beginning of the light period. IL-1 produced a marked increase in body temperature, which was significantly lower in E rats than in N and P rats. In a second experiment, rats were administered either IL-1 (10 micrograms/kg, i.p.) or saline at the beginning of the dark period. IL-1 produced an initial transient hypothermia followed by a longer-lasting hyperthermia. During the hyperthermic phase, fever in the E rats was lower than in the P rats, but comparable to fever in the N rats. IL-1 significantly reduced motor activity, during both the hypothermic and hyperthermic phases. This effect was similar in all prenatal treatment groups. IL-1 also suppressed 24-h food consumption in N and P rats and water consumption in P rats, but it did not produce significant anorexia and adypsia in E rats. A third experiment demonstrated that IL-1 (2 micrograms/ kg, ip) significantly increased ACTH and corticosterone release in all prenatal treatment groups. IL-1-induced corticosterone secretion was attenuated in P offspring, compared to both E and N rats. Together, these findings indicate that exposure to ethanol in utero produces impairments in mechanisms that mediate the effects of IL-1 on body temperature (particularly during the light period) and ingestive behavior, but not on motor activity and pituitary-adrenal activation. In view of the adaptive role of IL-1-induced fever and anorexia, these impairments may contribute to the decreased resistance to infections observed in animals and humans following FAE.