IL-6 is essential in TNF-alpha -induced fever

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 1998-12, Vol.275 (6), p.2028-R2034
• Main Authors: Sundgren-Andersson, Anna K, Ostlund, Pernilla, Bartfai, Tamas
• Format: Article
• Language: English
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.1998.275.6.R2028

Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, S-10691 Stockholm, Sweden Tumor necrosis factor- (TNF- ) is a pleiotropic cytokine that orchestrates an array of local and systemic effects. For instance, acute exposure to a high dose of TNF- results in septic shock and fever. We have used interleukin-1 (IL-1 )- and interleukin-6 (IL-6)-deficient mice, along with their wild-type equivalents, to define a role for TNF- in fever. Briefly, the mice produced prostaglandin E 2 -dependent fevers in response to recombinant murine TNF- (rmTNF- ). Furthermore, rmTNF- (12 µg/mouse ip) triggered a febrile response in IL-1 -deficient mice as well as in their corresponding wild-type controls. In contrast, the IL-6-deficient mice were resistant to rmTNF- (4.5 µg/mouse ip), although their wild-type counterparts readily mounted a fever. In the IL-6-deficient mice, moreover, the febrile response to rmTNF- could be restored by a central administration of rat recombinant IL-6 (500 ng/mouse icv). We thus conclude that TNF- can trigger fever independent of IL-1 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- -induced fever. interleukin-1 ; interleukin-1 -deficient mice; interleukin-6-deficient mice; lipopolysaccharide; indomethacin