Exacerbated febrile responses to lps, but not turpentine, in tnf
double receptor knockout mice.
Leon, Lisa R., Wieslaw Kozak, Jacques Peschon, Matthew J. Kluger.
Institute for Basic and Applied Medical Research, The Lovelace
Institutes, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico 87108 and
Immunex Research and Development Corporation, 51 University Street,
Seattle, Washington 98101
APStracts 3:0312R, 1996.
We examined the effects of injections of systemic (lipopolysaccharide;
LPS; 2.5 mg/kg or 50 [mu]g/kg, ip) or local (turpentine; 100 [mu]l,
sc) inflammatory stimuli on fever, motor activity, body weight and
food intake in TNF double receptor (TNFR) knockout mice. A high dose
of LPS resulted in exacerbated fevers in TNFR knockout mice compared
to wildtype mice for the early phase of fever (3-15h); the late phase
of fever (16-24h) and fevers to a low dose of LPS were similar in
both groups. Motor activity, body weight and food intake were
similarly reduced in both groups of mice following LPS. In response
to turpentine, TNFR knockout and wildtype mice developed virtually
identical responses to all variables monitored. These results suggest
that (1) TNF modulates fevers to LPS dose-dependently, (2) TNF does
not modulate fevers to a sc injection of turpentine, and (3) knockout
mice may develop cytokine redundancy in the regulation of the APR to
ip injected LPS or sc injected turpentine.
Received 26 June 1996; accepted in final form 30 July 1996.
APS Manuscript Number R371-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996