Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1.
Interleukin 1 (IL-1) is a cytokine released during immune activation that mediates the host's response to infection and inflammation. Peripheral and central injections of IL-1 induce fever and sickness behavior, including decreased food motivation and reduced interest in social activities. To determine the receptor mechanisms responsible for these effects, rats were injected with IL-1 receptor antagonist (IL-1ra), an endogenous cytokine that acts as a pure antagonist of IL-1 receptors. IL-1ra blocked the increased body temperature and oxygen consumption induced by injection of recombinant human IL-1 only when both cytokines were administered i.p. In contrast, i.p. or intracerebroventricular administration of IL-1ra blocked the depressive effect of IL-1 beta on food-motivated behavior and social exploration when this cytokine was administered by the same route as the antagonist. In addition, intracerebroventricular IL-1ra blocked the reduction in social exploration produced by i.p. IL-1 beta but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1 beta. In each case, the dose of IL-1ra was 100- to 1000-fold in excess of the biologically active dose of IL-1. These results suggest that the receptor mechanisms that mediate the behavioral and pyrogenic effects of IL-1 are heterogeneous.
Kent
S
S
Institut National de la Recherche Agronomique-Institut National de la Santé et de la Recherche Médicale U176, Bordeaux, France.
Bluthe
R M
RM
Dantzer
R
R
Hardwick
A J
AJ
Kelley
K W
KW
Rothwell
N J
NJ
Vannice
J L
JL
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D011749:Pyrogens / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000494:pharmacology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011749:Pyrogens; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins