Prenatal Immune Stress in Rats Dampens Fever during Adulthood

Abstract

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.