Immunotolerant p50/NFκB Signaling and Attenuated Hepatic IFNβ Expression Increases Neonatal Sensitivity to Endotoxemia.

ABSTRACT: Sepsis is a major cause of neonatal morbidity and mortality. The current paradigm suggests that neonatal susceptibility to infection is explained by an innate immune response that is functionally immature. Recent studies in adults have questioned a therapeutic role for IFNβ in sepsis; however, the role of IFNβ in mediating neonatal sensitivity to sepsis is unknown. We evaluated the transcriptional regulation and expression of IFNβ in early neonatal (P0) and adult murine models of endotoxemia (IP LPS, 5 mg/kg). We found that hepatic, pulmonary, and serum IFNβ expression was significantly attenuated in endotoxemic neonates when compared to similarly exposed adults. Furthermore, endotoxemia induced hepatic p65/NFκB and IRF3 activation exclusively in adults. In contrast, endotoxemia induced im

SUBMITTER: McKenna S 

PROVIDER: S-EPMC6168645 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature