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Endocrinology. 2004 Nov;145(11):5044-8. Epub 2004 Jul 22.

Interleukin (IL)-6, but not IL-1, induction in the brain downstream of cyclooxygenase-2 is essential for the induction of febrile response against peripheral IL-1alpha.

Author information

1
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

Abstract

IL-1 is an endogenous pyrogen produced upon inflammation or infection. Previously, we showed that, upon injection with turpentine, IL-1 is induced in the brain in association with the development of fever. The role of endogenous IL-1 in the brain and the signaling cascade to activate thermosensitive neurons, however, remain to be elucidated. In this report, febrile response was analyzed after peripheral injection of IL-1alpha. We found that a normal febrile response was induced even in IL-1alpha/beta-deficient mice, indicating that production of IL-1 in the brain is not necessarily required for the response. In contrast, IL-6-deficient mice did not exhibit a febrile response. Cyclooxygenase (Cox)-2 expression in the brain was strongly induced 1.5 h after injection of IL-1alpha, whereas IL-6 expression was observed 3 h after the injection. Cox-2 expression in the brain was not influenced by IL-6 deficiency, whereas indomethacin, an inhibitor of cyclooxygenases, completely inhibited induction of IL-6. These observations suggest a mechanism of IL-1-induced febrile response in which IL-1 in the blood activates Cox-2, with the resulting prostaglandin E(2) inducing IL-6 in the brain, leading to the development of fever.

PMID:
15271886
DOI:
10.1210/en.2004-0054
[Indexed for MEDLINE]

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