Peripheral TNFalpha, but not peripheral IL-1, requires endogenous IL-1 or TNFalpha induction in the brain for the febrile response.
It is known that peripherally administered IL-1 and TNFalpha induce fever through mechanisms involving prostaglandin (PG)E2. In this report, we compared the signaling cascade induced in the brain by TNFalpha and IL-1. Peripheral administration of TNFalpha-induced enhanced fever in IL-1 Receptor antagonist KO mice, suggesting that IL-1 is involved in the TNFalpha mediated fever. IL-1alpha, but not TNFalpha, induced fever in IL-1alpha/beta/TNFalpha KO mice, although central administration of TNFalpha-induced fever. Only IL-1alpha, but not TNFalpha, induced IL-6 in the IL-1alpha/beta/TNFalpha KO mouse brain, while both cytokines induced cyclooxygenase (Cox)-2. I.c.v. administration of PGE2 induced only transient fever in contrast to the TNFalpha- or IL-1alpha-induced fever that lasted longer. Taken together, either IL-1 or TNFalpha induction in the brain is required for the response induced by TNFalpha but not by IL-1alpha, and that both Cox-2 and IL-6 induction are required for prolonged febrile response against these cytokines.
Chida
Dai
D
Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Iwakura
Yoichiro
Y
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000187:drug effects* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced* / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha