TNF SOLUBLE RECEPTOR AND ANTISERUM AGAINST TNF ENHANCE LIPOPOLYSACCHARIDE FEVER IN MICE

We tested the effects of tumor necrosis factor (TNF) soluble receptor (sTNFR) and anti-TNF serum (anti-TNF) administered intraperitoneally on fever induced by lipopolysaccharide (LPS) in mice. Both agents have been shown to block bioactivity of mouse TNF-alpha. Core temperature (T-b) and locomotor activity in unrestrained mice were measured by biotelemetry. Within 1 h from the LPS injection (2.5 mg/kg ip) T-b decreased below normal for 5-6 h and motor activity was depressed for the following 48 h. After this initial reduction, T-b increased and reached a peak at similar to 24 h postinjection. Anti-TNF and sTNFR blocked this ''hypothermic phase'' after LPS, and the fevers started sooner; however, the levels and time of peak temperature did not change markedly. In addition, a human recombinant TNF-alpha, given intraperitoneally abolished fever and prolonged the fall of T-b in mice after LPS. We conclude that the reduction of T-b soon after injection of LPS in mice is dependent on TNF-alpha.