Hyperresponsive febrile reactions to interleukin (IL) 1α and IL-1β, and altered brain cytokine mRNA and serum cytokine levels, in IL-1β-deficient mice
Autor: | Katarina Alheim, C. A. Dinarello, P. Ghezzi, E. Di Santo, Homa Hasanvan, Zhen Chai, Tamas Bartfai, David Malinowsky, Giamila Fantuzzi |
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Rok vydání: | 1997 |
Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Fever Transcription Genetic Lipopolysaccharide medicine.medical_treatment Hypothalamus Polymerase Chain Reaction Body Temperature Proinflammatory cytokine Mice chemistry.chemical_compound Corticosterone Internal medicine Escherichia coli medicine Animals RNA Messenger Interleukin 6 Mice Knockout Multidisciplinary biology Janus kinase 1 Interleukin-6 Tumor Necrosis Factor-alpha Brain Receptors Interleukin-1 Interleukin Biological Sciences Recombinant Proteins Circadian Rhythm Cytokine Endocrinology chemistry Immunology biology.protein Cytokines Tumor necrosis factor alpha Interleukin-1 |
Zdroj: | Proceedings of the National Academy of Sciences. 94:2681-2686 |
ISSN: | 1091-6490 0027-8424 |
Popis: | 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. |
Databáze: | OpenAIRE |
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