Journal Article

Different Receptor Mechanisms Mediate the Pyrogenic and Behavioral Effects of Interleukin 1

Hardwick, Anthea J., Kent, Stephen, Vannice, James L., Dantzer, Robert, Kelley, Keith W., Bluthe, Rose-Marie, Rothwell, Nancy J.

1992

Overview

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-1β 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-1β but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1β. 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.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences
• Subject: Analysis of the immune response. Humoral and cellular immunity / Animal behavior / Animals / Biological and medical sciences / Body Temperature Regulation - drug effects / Cerebral Ventricles - drug effects / Cerebral Ventricles - physiology / Cytokines / Dosage / Exploratory Behavior - drug effects / Feeding Behavior - drug effects / Fever / Fundamental and applied biological sciences. Psychology / Fundamental immunology / Human resources / Immunobiology / Infections / Injections, Intraperitoneal / Injections, Intraventricular / interleukin 1 / Interleukin 1 Receptor Antagonist Protein / Interleukin-1 - administration & dosage / Interleukin-1 - pharmacology / Interleukins / Life Sciences / Lymphokines, interleukins ( function, expression) / Male / mechanisms / Mice / Neurology / Oxygen Consumption - drug effects / Pretreatment / Proteins / pyrogenicity / pyrogens / Pyrogens - administration & dosage / Pyrogens - pharmacology / Rats / Rats, Sprague-Dawley / Rats, Wistar / Receptors / Receptors, Interleukin-1 - drug effects / Receptors, Interleukin-1 - physiology / Recombinant Proteins - administration & dosage / Recombinant Proteins - pharmacology / Regulatory factors and their cellular receptors / Rodents / Routes of administration / Sialoglycoproteins - administration & dosage / Sialoglycoproteins - pharmacology / Thermogenesis