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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-11-24
pubmed:abstractText
The role of intereukin-1 (IL-1) in mortality caused by endotoxaemia remains controversial. While IL-1 receptor antagonist (IL-1Ra) protects mice from lethal endotoxaemia, mice deficient in IL-1? (IL-1??(?/)?) display normal susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify the source of these discrepancies. Mice deficient in IL-1?, IL-1? or IL-1R type I were injected intraperitoneally with Escherichia coli or Salmonella typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild-type mice. In addition, serum cytokine concentrations were determined after LPS challenge and in vitro cytokine production by peritoneal macrophages was analysed. Clearance of radioactive IL-1? was examined in IL-1??(/)? and wild-type mice. IL-1??(/)? mice were normally susceptible to endotoxaemia and cytokine production did not differ from that in control mice. Surprisingly, LPS mortality in IL-1??(/)? mice was significantly greater than that in control mice, accompanied by higher interferon-? release. These effects were mediated by a distorted homeostasis of IL-1RI receptors, as shown by a strongly delayed clearance of IL-1?. In contrast to the IL-1??(/)? and IL-1??(/)? mice, IL-1RI?(/)? mice were completely resistant to high doses of LPS. In conclusion, IL-1RI-mediated signals are crucial in mediating mortality occurring as a result of lethal endotoxaemia. Investigation of IL-1-mediated pathways in IL-1 knock-out mice is complicated by a distorted homeostasis of IL-1Rs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1600-0463
pubmed:author
pubmed:copyrightInfo
© 2010 The Authors. APMIS © 2010 APMIS.
pubmed:issnType
Electronic
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1000-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Differential susceptibility to lethal endotoxaemia in mice deficient in IL-1?, IL-1? or IL-1 receptor type I.
pubmed:affiliation
Department of Medicine, Radboud University Nijmegen Medical Center, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't