IL-6 is essential in TNF-alpha-induced fever.
Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that orchestrates an array of local and systemic effects. For instance, acute exposure to a high dose of TNF-alpha results in septic shock and fever. We have used interleukin-1beta (IL-1beta)- and interleukin-6 (IL-6)-deficient mice, along with their wild-type equivalents, to define a role for TNF-alpha in fever. Briefly, the mice produced prostaglandin E2-dependent fevers in response to recombinant murine TNF-alpha (rmTNF-alpha). Furthermore, rmTNF-alpha (12 microgram/mouse ip) triggered a febrile response in IL-1beta-deficient mice as well as in their corresponding wild-type controls. In contrast, the IL-6-deficient mice were resistant to rmTNF-alpha (4.5 microgram/mouse ip), although their wild-type counterparts readily mounted a fever. In the IL-6-deficient mice, moreover, the febrile response to rmTNF-alpha could be restored by a central administration of rat recombinant IL-6 (500 ng/mouse icv). We thus conclude that TNF-alpha can trigger fever independent of IL-1beta but dependent on IL-6. We also suggest that central, rather than peripheral, IL-6 (plasma IL-6 was measured 2 h after pyrogenic challenge) is essential in TNF-alpha-induced fever.
Sundgren-Andersson
A K
AK
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, S-10691 Stockholm, Sweden.
Ostlund
P
P
Bartfai
T
T
D000818:Animals; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology*; D006801:Humans; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha