R. Yirmiya et al., EFFECTS OF FETAL ALCOHOL EXPOSURE ON FEVER, SICKNESS BEHAVIOR, AND PITUITARY-ADRENAL ACTIVATION-INDUCED BY INTERLEUKIN-1-BETA IN YOUNG-ADULT RATS, Brain, behavior, and immunity, 10(3), 1996, pp. 205-220
Exposure to alcohol in utero can lead to long-lasting impairments of i
mmune functions and to decreased resistance to infectious agents. We h
ave previously reported that fetal alcohol-exposed rats show markedly
decreased lipopolysaccharide-induced fever and suggested that fetal al
cohol exposure (FAE) impairs the communication between the immune and
the nervous systems. The present study examined the effects of interle
ukin-1 beta (IL-1) on body temperature, motor activity, ingestive beha
vior, and pituitary-adrenal activation in fetal alcohol-exposed and co
ntrol rats. Transmitters for continuous biotelemetric recording of bod
y temperature and motor activity were implanted ip 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 i
njected with either IL-I (2 mu g/kg, ip) 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 s
econd experiment, rats were administered either IL-1 (10 mu g/kg, ip)
or saline at the beginning of the dark period. IL-I produced an initia
l transient hypothermia followed by a longer-lasting hyperthermia. Dur
ing 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 redu
ced motor activity, during both the hypothermic and hyperthermic phase
s. This effect was similar in all prenatal treatment groups. IL-1 also
suppressed 24-h food consumption in N and P rats and water consumptio
n in P rats, but it did not produce significant anorexia and adypsia i
n E rats. A third experiment demonstrated that IL-1 (2 mu g/ kg, ip) s
ignificantly increased ACTH and corticosterone release in all prenatal
treatment groups. IL-l-induced corticosterone secretion was attenuate
d in P offspring, compared to both E and N rats. Together, these findi
ngs indicate that exposure to ethanol in utero produces impairments in
mechanisms that mediate the effects of IL-1 on body temperature (part
icularly during the light period) and ingestive behavior, but not on m
otor activity and pituitary-adrenal activation. In view of the adaptiv
e role of IL-l-induced fever and anorexia, these impairments may contr
ibute to the decreased resistance to infections observed in animals an
d humans following FAE. (C) 1996 Academic Press, Inc.