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Hyperresponsive febrile reactions to interleukin (IL) 1alpha and IL-1beta, and altered brain cytokine mRNA and serum cytokine levels, in IL-1beta-deficient mice.

Abstract
IL-1beta is an endogenous pyrogen that is induced during systemic lipopolysaccharide (LPS)- or IL-1-induced fever. We have examined the fever and cytokine responses following i.p. injection of IL-1 agonists, IL-1alpha and IL-1beta, and compared these with response to LPS (i.p.) in wild-type and IL-1beta-deficient mice. The IL-1beta deficient mice appear to have elevated body temperature but exhibit a normal circadian temperature cycle. Exogenously injected IL-1beta, IL-1alpha, or LPS induced hyperresponsive fevers in the IL-1beta-deficient mice. We also observed phenotypic differences between wild-type and IL-1beta-deficient mice in hypothalamic basal mRNA levels for IL-1alpha and IL-6, but not for IL-1beta-converting enzyme or IL-1 receptor type I or type II. The IL-1alpha mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-1beta-deficient mice as compared with wild-type mice. The IL-1beta-deficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type alpha levels than the wild-type mice. The data suggest that, in the redundant cascade of proinflammatory cytokines, IL-1beta plays an important but not obligatory role in fever induction by LPS or IL-1alpha, as well as in the induction of serum tumor necrosis factor type alpha and corticosterone responses either by LPS or by IL-1alpha or IL-1beta.
AuthorsK Alheim, Z Chai, G Fantuzzi, H Hasanvan, D Malinowsky, E Di Santo, P Ghezzi, C A Dinarello, T Bartfai
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 94 Issue 6 Pg. 2681-6 (Mar 18 1997) ISSN: 0027-8424 [Print] United States
PMID9122256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Corticosterone
Topics
  • Animals
  • Body Temperature (drug effects)
  • Brain (immunology)
  • Circadian Rhythm
  • Corticosterone (blood)
  • Cytokines (biosynthesis, blood)
  • Escherichia coli
  • Fever (immunology)
  • Hypothalamus (immunology)
  • Interleukin-1 (biosynthesis, deficiency, pharmacology)
  • Interleukin-6 (biosynthesis)
  • Lipopolysaccharides (toxicity)
  • Male
  • Mice
  • Mice, Knockout
  • Polymerase Chain Reaction
  • RNA, Messenger (biosynthesis)
  • Receptors, Interleukin-1 (biosynthesis)
  • Recombinant Proteins (pharmacology)
  • Transcription, Genetic (drug effects)
  • Tumor Necrosis Factor-alpha (metabolism)

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