Peripheral TNFα, but not peripheral IL-1, requires endogenous IL-1 or TNFα induction in the brain for the febrile response

It is known that peripherally administered IL-1 and TNFα induce fever through mechanisms involving prostaglandin (PG)E2. In this report, we compared the signaling cascade induced in the brain by TNFα and IL-1. Peripheral administration of TNFα-induced enhanced fever in IL-1 Receptor antagonist KO mice, suggesting that IL-1 is involved in the TNFα mediated fever. IL-1α, but not TNFα, induced fever in IL-1α/β/TNFα KO mice, although central administration of TNFα-induced fever. Only IL-1α, but not TNFα, induced IL-6 in the IL-1α/β/TNFα KO mouse brain, while both cytokines induced cyclooxygenase (Cox)-2. Icv administration of PGE2 induced only transient fever in contrast to the TNFα- or IL-1α-induced fever that lasted longer. Taken together, either IL-1 or TNFα induction in the brain is required for the response induced by TNFα but not by IL-1α, and that both Cox-2 and IL-6 induction are required for prolonged febrile response against these cytokines.