a-controlled-mouse-model-for-neonatal-polymicrobial-sepsis

A Controlled Mouse Model for Neonatal Polymicrobial Sepsis

Neonatal sepsis remains a global burden. A preclinical model to screen effective prophylactic or therapeutic interventions is needed. Neonatal mouse ...

University of Florida

Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis.

Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

Limited achievement of NIH research independence by pediatric K award recipients.

Sepsis disproportionately affects the very old and the very young. IL-1 signaling is important in innate host defense but may also play a deleterious role in acute inflammatory conditions (including sepsis) by promulgating life-threatening inflammation. IL-1 signaling is mediated by two distinct ligands: IL-1α and IL-1β, both acting on a common receptor (IL-1R1). IL-1R1 targeting has not reduced adult human sepsis mortality despite biologic plausibility. Because the specific role of IL-1α or IL-1β in sepsis survival is unknown in any age group and the role of IL-1 signaling remains unknown in neonates, we studied the role of IL-1 signaling, including the impact of IL-1α and IL-1β, on neonatal murine sepsis survival. IL-1 signaling augments the late plasma inflammatory response to sepsis. IL-1α and not IL-1β is the critical mediator of sepsis mortality, likely because of paracrine actions within the tissue. These data do not support targeting IL-1 signaling in neonates.

Article	Year
Histological chorioamnionitis shapes the neonatal transcriptomic immune response. Early human development\| PubMed ID: 27318328	2016
Limited achievement of NIH research independence by pediatric K award recipients. Pediatric research\| PubMed ID: 29904137	2018
Cutting Edge: IL-1α and Not IL-1β Drives IL-1R1-Dependent Neonatal Murine Sepsis Lethality. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 30305325	2018

James Wynn

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