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 o n 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 biot elemetry. Within 1 h from the LPS injection (2.5 mg/kg ip) T-b decreas ed below normal for 5-6 h and motor activity was depressed for the fol lowing 48 h. After this initial reduction, T-b increased and reached a peak at similar to 24 h postinjection. Anti-TNF and sTNFR blocked thi s ''hypothermic phase'' after LPS, and the fevers started sooner; howe ver, the levels and time of peak temperature did not change markedly. In addition, a human recombinant TNF-alpha, given intraperitoneally ab olished fever and prolonged the fall of T-b in mice after LPS. We conc lude that the reduction of T-b soon after injection of LPS in mice is dependent on TNF-alpha.