Anorexia induced by cytokine interactions at pathophysiological
concentrations .
Sonti, Gayatri, Sergey E. Ilyin, and Carlos R. Plata-Salam[acute]an.
School of Life and Health Sciences, University of Delaware, Newark,
Delaware 19716-2590, U.S.A.
APStracts 3:0044R, 1996.
Interleukin-1[beta] (IL-1[beta]), IL-8 and tumor necrosis factor
-[alpha] (TNF-[alpha]) induce anorexia when administered
intracerebroventricularly (ICV) at estimated pathophysiological
concentrations reported in the cerebrospinal fluid (CSF). Our
hypothesis is that pivotal cytokines released during pathological
processes interact to induce anorexia during disease. In the present
study, we investigated the effects of the ICV microinfusion of
individual or multiple combinations (8 dyads and 5 triads) of IL
-1[beta], IL-8 and TNF-[alpha] on feeding and the microstructure of
eating in rats maintained ad libitum. Estimated pathophysiological
concentrations of cytokine combinations exhibited additive or
synergistic activities in inducing anorexia. Computerized analysis of
behavioral patterns demonstrated that the most effective treatment
(triad of 1.0 ng IL-1[beta] plus 20 ng IL-8 plus 20 ng TNF
-[alpha]/rat, n=11) decreased nighttime meal size by 42% and feeding
rate (meal size/meal duration) by 26%, while increased the satiety
ratio (postprandial intermeal intervals/meal size) by 80%; meal
duration and meal frequency were not significantly affected. Analysis
of meal parameters into 4-h intervals revealed a maximum effect
during the first 4-h interval after the ICV administration. The time
course during this initial 4-h interval analyzed in 10 min periods
was similar for IL-8 (n=10) and TNF-[alpha] (n=11), and both were
significantly different from the time course induced by IL-1[beta]
(n=10) and the most effective triad (n=11). ICV microinfusion of
heat-inactivated triad or intraperitoneal administration of the most
effective triad, in doses equivalent to those administered centrally,
had no effect on feeding. The results suggest that estimated
pathophysiological concentrations of cytokines in the CSF act
centrally and additively or synergistically to decrease feeding and
this effect may participate in the anorexia frequently accompanying
pathological processes.
Received 24 October 1995; accepted in final form 1 February 1996.
APS Manuscript Number R663-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96