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Cutting Edge: IL-1α and Not IL-1β Drives IL-1R1-Dependent Neonatal Murine Sepsis Lethality
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 201(10)
- Publication Year :
- 2018
-
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-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.
- Subjects :
- 0301 basic medicine
Male
Sepsis mortality
Inflammatory response
Immunology
Interleukin-1beta
Inflammation
Article
Sepsis
03 medical and health sciences
Paracrine signalling
Mice
0302 clinical medicine
Mediator
Interleukin-1alpha
medicine
Immunology and Allergy
Animals
Humans
Receptor
Receptors, Interleukin-1 Type I
business.industry
Infant, Newborn
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
Animals, Newborn
Lethality
Female
medicine.symptom
business
030215 immunology
Signal Transduction
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 201
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....e587d0118396523433b5d6ccfc046650