Department of Physiology, Kuwait University, Safat, Kuwait.
Dev Neurosci. 2012;34(4):318-26. doi: 10.1159/000339852. Epub 2012 Jul 20.
Fever is a major component of the host's defense against infection. Inadequate febrile response can predispose an individual to the deleterious effects of infection. Neonatal exposure to infectious agents such as bacterial lipopolysaccharide (LPS) permanently dampens the adult febrile response. Whether prenatal immune challenge alters febrile response during adulthood is still not known. In the present study, LPS (100 µg/kg, i.p.) or pyrogen-free saline was administered to pregnant rats on either gestation day (GD) 12, 15 or 19 and the febrile response of their respective adult offspring was monitored. During adulthood (>70 days old), the rats born to LPS-injected dams on GD15 displayed a significantly attenuated febrile response to LPS (50 µg/kg, i.p.) compared to their control counterparts born to dams given saline on GD15. Immune challenge during either early (GD12) or late (GD19) pregnancy did not have a significant impact on fever in the adult offspring. Immune challenge on GD15, but not on GD12 or 19, heightened the plasma corticosterone response to a subsequent LPS injection to the adult offspring but did not have a significant effect on their basal plasma corticosterone levels. Finally, LPS-induced COX-2 in the fever-controlling regions of the hypothalamus was significantly reduced in the adult rats born to dams given LPS on GD15 compared to their counterparts born to dams given saline on GD15. Such COX-2 reduction was not observed in the adult offspring born to dams given LPS on either GD12 or 19. Taken together, these data suggest that a single immune challenge during a critical window of pregnancy alters the neuroimmune response in adult offspring.
发热是宿主抗感染的主要防御机制。发热反应不足可使个体易受感染的有害影响。新生儿暴露于细菌脂多糖（LPS）等感染因子会永久抑制成年后的发热反应。目前尚不清楚产前免疫挑战是否会改变成年后的发热反应。在本研究中，在妊娠第 12、15 或 19 天向怀孕大鼠腹腔内注射 LPS（100μg/kg）或无热原生理盐水，并监测其各自成年后代的发热反应。在成年期（>70 天大），出生于妊娠第 15 天接受 LPS 注射的母鼠的大鼠对 LPS（50μg/kg，腹腔内）的发热反应明显减弱，而出生于妊娠第 15 天接受生理盐水的母鼠的大鼠则没有。在妊娠早期（GD12）或晚期（GD19）进行免疫挑战对成年后代的发热没有显著影响。在 GD15 进行免疫挑战，但不在 GD12 或 19 进行免疫挑战，会增加成年后代对随后 LPS 注射的血浆皮质酮反应，但对其基础血浆皮质酮水平没有显著影响。最后，与出生于接受生理盐水的母鼠的大鼠相比，出生于接受 LPS 的母鼠的 GD15 的下丘脑控制发热区域的 LPS 诱导的 COX-2 显著减少。在出生于接受 LPS 的母鼠的 GD12 或 19 的成年后代中未观察到这种 COX-2 减少。总之，这些数据表明，妊娠关键窗口期的单次免疫挑战会改变成年后代的神经免疫反应。
