Cutting Edge: IL-1? and Not IL-1? Drives IL-1R1-Dependent Neonatal Murine Sepsis Lethality.

ABSTRACT: 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-1? and IL-1?, 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-1? or IL-1? 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-1? and IL-1?, on neonatal murine sepsis survival. IL-1 signaling augments the late plasma inflammatory response to sepsis. IL-1? and not IL-1? 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.

SUBMITTER: Benjamin JT 

PROVIDER: S-EPMC6219910 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature