TUMOR-NECROSIS-FACTOR-ALPHA AND FEVER AFTER PERIPHERAL INFLAMMATION IN THE RAT

The involvement of endogenous tumor necrosis factor-alpha (TNF-alpha) in the pyrogenic [i.e., rise in colonic temperature (T-c)] and thermog enic [increase in oxygen consumption (VO2)] responses to inflammation was investigated in rats subjected to an intramuscular injection of tu rpentine. Turpentine administration caused a rise in T-c and VO2 withi n 2 h (0.9 +/- 0.1 degrees C, 27 +/- 2%, respectively). Eighteen to tw enty hours after turpentine, the magnitude of these responses had incr eased (2.3 degrees C fever and a 28% increase in metabolic rate compar ed with control animals) and was associated with marked inflammation i n the injected limb. A rapid (by 4 h) and sustained rise in the plasma concentration of the endogenous pyrogen IL-6, but not TNF-alpha, was also observed. Intravenous pretreatment with a TNF-(a)lpha antiserum a ttenuated the rise in T-c observed 2, 8, and 18 h after turpentine inj ection and almost abolished the hypermetabolic response observed at 18 h. In addition, the TNF-alpha antiserum inhibited the peak rise (8 h) in plasma IL-6 by 76%. These findings indicate that endogenous TNF-al pha is involved in fever and hypermetabolism during inflammation and t hat it may exert these effects by inducing the release of IL-6 into ci rculation.