Innate immune dysfunction in the neonatal rat following prenatal endotoxin exposure

Abstract

The efficacy of the neonatal innate immune system to respond to bacterial exposure following maternal infection is of great interest, as the neonatal period is one of relative immune immaturity, and is associated with high rates of morbidity and mortality. This study aimed to determine the response to an in-vivo endotoxin challenge in the neonatal period following prenatal exposure to bacterial endotoxin. Pregnant Fischer 344 dams received either endotoxin or the vehicle on gestational days 16, 18 and 20 (term=23 days). The neonatal (5 day) offspring were then exposed to an endotoxin challenge; blood was collected at baseline or at 4 h for analysis of blood cell counts, corticosterone, TNF alpha and IL-1 beta, levels. The neonatal rat pups responded to the challenge with significantly reduced corticosterone, TNF alpha and IL-1 beta levels compared to controls (p<0.003). Monocyte, neutrophil and eosinophil counts were also significantly reduced in the prenatal endotoxin offspring compared to controls (p<0.02). While the immune system is functionally immature in the neonatal period, these results suggest that prenatal infection may further reduce the capacity of the innate neonatal immune system to respond to endotoxin, leaving offspring more vulnerable to pathogenic invasion in neonatal life.