AJP - Endocrinology and Metabolism, Vol 256, Issue 1 E111-E115, Copyright © 1989 by American Physiological Society

ARTICLES

CRF is involved in the pyrogenic and thermogenic effects of interleukin 1 beta in the rat

N. J. Rothwell
Department of Physiological Sciences, University of Manchester, United Kingdom.

Interleukin 1 beta (IL-1 beta) is an endogenous peptide that induces fever, largely by central stimulation of sympathetically mediated thermogenesis. Microinjection (icv) of human recombinant IL-1 beta (50 ng) caused acute (response within 60 min) increases in colonic temperature (1.8 degrees C), oxygen consumption (Vo2; 36%), white blood cell count (96%), and brown adipose tissue (BAT) activity (mitochondrial GDP binding, 129%) in conscious rats. All of these effects were prevented or markedly inhibited by prior injection (icv) of an antagonist to corticotropin-releasing factor (CRF) [alpha-helical CRF-(9-41), 25 micrograms] and reduced by pretreatment with purified antibody to CRF. Injection of endotoxin (2 mg/kg ip), human recombinant tumor necrosis factor-alpha (TNF alpha; 5 micrograms icv) or prostaglandin E2 (PGE2; 100 ng icv) all stimulated body temperature (0.9-1.6 degrees C) and Vo2 (18-25%); TNF alpha did not affect white blood cell count but increased BAT activity by 38%. Prior injection of the CRF antagonist did not modify the actions of endotoxin, TNF alpha, or PGE2. Central injection of CRF (4 micrograms) produced a 23% increase in metabolic rate, which was unaffected by injection of the cycloxygenase inhibitor ibuprofen (5 mg/kg ip). These data indicate that the central effects of interleukin 1 beta on metabolic rate, body temperature, BAT activity, and white blood cell count are all mediated by release of CRF. The thermogenic effects of endotoxin, TNF alpha, and PGE2 are not dependent on CRF.

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