Yirmiya R, Tio D L, Taylor A N
Department of Psychology, Hebrew University of Jerusalem, Mount Scopus, Israel.
Brain Behav Immun. 1996 Sep;10(3):205-20. doi: 10.1006/brbi.1996.0019.
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.
子宫内接触酒精会导致免疫功能的长期损害，并降低对感染因子的抵抗力。我们之前报道过，暴露于酒精的胎儿大鼠脂多糖诱导的发热明显降低，并提示胎儿酒精暴露（FAE）会损害免疫系统与神经系统之间的通讯。本研究检测了白细胞介素-1β（IL-1）对暴露于酒精的胎儿大鼠和对照大鼠的体温、运动活动、摄食行为以及垂体-肾上腺激活的影响。将用于连续生物遥测记录体温和运动活动的发射器经腹腔注射植入正常（N）成年大鼠、喂食添加乙醇的液体饲料的母鼠后代（E）以及配对喂食的对照后代（P）体内。在一个实验中，在光照期开始时给大鼠注射IL-1（2微克/千克，腹腔注射）或生理盐水。IL-1使体温显著升高，E组大鼠的体温显著低于N组和P组大鼠。在第二个实验中，在黑暗期开始时给大鼠注射IL-1（10微克/千克，腹腔注射）或生理盐水。IL-1最初引起短暂的体温过低，随后是持续时间更长的体温过高。在体温过高阶段，E组大鼠的发热低于P组大鼠，但与N组大鼠的发热相当。在体温过低和体温过高阶段，IL-１均显著降低运动活动。所有产前治疗组的这种效应相似。IL-1还抑制了N组和P组大鼠24小时的食物消耗以及P组大鼠的水消耗，但未在E组大鼠中产生明显的厌食和烦渴。第三个实验表明，IL-1（2微克/千克，腹腔注射）在所有产前治疗组中均显著增加促肾上腺皮质激素（ACTH）和皮质酮的释放。与E组和N组大鼠相比，P组后代中IL-1诱导的皮质酮分泌减弱。总之，这些发现表明子宫内接触乙醇会损害介导IL-1对体温（尤其是在光照期）和摄食行为影响的机制，但不会损害运动活动和垂体-肾上腺激活。鉴于IL-1诱导的发热和厌食的适应性作用，这些损害可能导致在FAE后的动物和人类中观察到的对感染抵抗力下降。
