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.
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Authors | K Alheim, Z Chai, G Fantuzzi, H Hasanvan, D Malinowsky, E Di Santo, P Ghezzi, C A Dinarello, T Bartfai |
Journal | Proceedings 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 |
PMID | 9122256
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cytokines
- Interleukin-1
- Interleukin-6
- Lipopolysaccharides
- RNA, Messenger
- Receptors, Interleukin-1
- Recombinant Proteins
- Tumor Necrosis Factor-alpha
- Corticosterone
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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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