Neonatal programming of the rat neuroimmune response: stimulus specific changes elicited by bacterial and viral mimetics.

Recently, it has been shown that the neonatal immune environment can have significant programming effects on the adult neuroimmune response. A single neonatal immune challenge with the bacterial mimetic lipopolysaccharide (LPS) can alter the neuroendocrine, neurochemical and febrile responses to a subsequent, homotypic (LPS) immune challenge as adults. As the programming effects of viral stimuli during this neonatal period are unknown, we tested whether the viral mimetic polyinosinic-polycytidylic acid (PolyIC), administered on postnatal day 14 (P14) would alter the adult neuroimmune responses to a subsequent PolyIC challenge. Our results show that animals treated neonatally with PolyIC had significantly attenuated febrile responses to an adult PolyIC challenge, which coincided with a heightened corticosteroid response. When the corticosteroid receptor blocker RU486 was administered prior to the adult PolyIC challenge, animals treated neonatally with PolyIC no longer displayed attenuated febrile responses. Similar responses to an adult LPS challenge have been seen in animals that were exposed neonatally to LPS, indicating that both neonatal immune stimuli elicit highly similar programming effects on the adult neuroimmune responses. However, we find that neither neonatal PolyIC nor neonatal LPS challenges led to an alteration in the adult febrile or corticosteroid responses to a heterotypic adult immune challenge, indicating that the programming effects of the neonatal immune environment are stimulus specific, and do not alter the adult responses to other immune stimuli.