Anorexic but not pyrogenic actions of interleukin-1 are modulated by central melanocortin-3/4 receptors in the rat.
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.
Lawrence
C B
CB
School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. catherine.b.lawrence@man.ac.uk
Rothwell
N J
NJ
D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004435:Eating / Q000187:drug effects; D005334:Fever / Q000139:chemically induced; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000494:pharmacology; D011749:Pyrogens / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018043:Receptors, Corticotropin / Q000819:agonists / Q000502:physiology*; D044101:Receptors, Melanocortin; D015431:Weight Loss / Q000187:drug effects; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D001067:Appetite Depressants; D007375:Interleukin-1; D011749:Pyrogens; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones