Tumor necrosis factor soluble receptor and antiserum against tumor
necrosis factor enhance lipopolysaccharide fever in mice.
Kozak, Wieslaw, Carole A. Conn, John J. Klir, Grace H. W. Wong,
Matthew J. Kluger.
Institute for Basic and Applied Medical Research, The Lovelace
Institutes, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico 87108,
Department of Molecular Biology, Genentech, Inc., South San
Francisco, California 94080
APStracts 2:0031R, 1995.
We tested the effects of TNF soluble receptor (sTNFR) and anti-TNF
serum (Anti-TNF) administered intraperitoneally (ip) 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 24
h postinjection. Anti-TNF and sTNFR blocked this "hypothermic phase"
following 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 ip abolished fever and prolonged the
fall of Tb in mice following LPS. We conclude that the reduction of
Tb soon after injection of LPS in mice is dependent on TNF[alpha].
Received 12 July 1994; accepted in final form 22 January 1995.
APS Manuscript Number R375-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.