Anorexic but Not Pyrogenic Actions of interleukin-1 Are Modulated by Central melanocortin-3/4 Receptors in the Rat

J Neuroendocrinol. 2001 Jun;13(6):490-5. doi: 10.1046/j.1365-2826.2001.00660.x.


The cytokine interleukin-1 (IL-1), which mediates many responses to infection and injury, induces anorexia and fever through direct actions in the central nervous system. The melanocortin neuropeptides, such as alpha melanocyte-stimulating hormone (alpha-MSH), reportedly antagonize many actions of IL-1, including fever and anorexia. However, it is unknown whether endogenous melanocortins modulate anorexia induced by IL-1. The objective of the present study was to establish the effect of endogenous melanocortins on IL-1-induced anorexia and fever in the rat. Intracerebroventricular (i.c.v.) injection of IL-1beta caused a significant reduction in food intake and body weight gain, and a rise in core body temperature in conscious rats. Coadministration of the melanocortin-3/4 receptor (MC3/4-R) antagonist, SHU9119, reversed IL-1beta-induced reductions in food intake and body weight, but did not affect the febrile response to IL-1beta. These data suggest IL-1beta may elicit its effects on food intake through the melanocortin system, predominantly via the MC3-R or MC4-R. In contrast, IL-1beta-induced fever does not appear to be mediated or modulated by MC3-R or MC4-R activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / chemically induced
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / pharmacology*
  • Body Temperature / drug effects
  • Brain / drug effects*
  • Brain / physiology
  • Eating / drug effects
  • Fever / chemically induced
  • Injections, Intraventricular
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / pharmacology*
  • Kinetics
  • Male
  • Melanocyte-Stimulating Hormones / administration & dosage
  • Melanocyte-Stimulating Hormones / pharmacology
  • Pyrogens / administration & dosage
  • Pyrogens / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin / agonists
  • Receptors, Corticotropin / physiology*
  • Receptors, Melanocortin
  • Weight Loss / drug effects
  • alpha-MSH / administration & dosage
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / pharmacology


  • Appetite Depressants
  • Interleukin-1
  • Pyrogens
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-
  • SHU 9119
  • alpha-MSH
  • Melanocyte-Stimulating Hormones