AJP - Regulatory, Integrative and Comparative Physiology, Vol 269, Issue 1 23-R29, Copyright © 1995 by American Physiological Society
TNF soluble receptor and antiserum against TNF enhance lipopolysaccharide fever in mice
W. Kozak, C. A. Conn, J. J. Klir, G. H. Wong and M. J. Kluger
Institute for Basic and Applied Medical Research, Lovelace Institutes, Albuquerque, New Mexico 87108, USA.
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 (Tb) and
locomotor activity in unrestrained mice were measured by biotelemetry.
Within 1 h from the LPS injection (2.5 mg/kg ip) Tb decreased below normal
for 5-6 h and motor activity was depressed for the following 48 h. After
this initial reduction, Tb increased and reached a peak at approximately 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
Tb in mice after LPS. We conclude that the reduction of Tb soon after
injection of LPS in mice is dependent on TNF-alpha.
