Involvement of the arcuate nucleus of the hypothalamus in interleukin-1-induced anorexia.
Cytokine-mediated anorexia is a component of "sickness behavior" and presents a significant obstacle in the treatment of chronic illnesses. We hypothesized an involvement of the hypothalamic arcuate nucleus (ARH) in mediating the anorexic effects of a systemic interleukin-1 (IL-1) challenge based on its content of peptidergic neurons involved in feeding, its expression of IL-1 receptors and its sensitivity to systemic IL-1. IL-1 (6 microg/kg, i.v.) was found to induce Fos expression in both pro-opiomelanocortin- and neuropeptide Y-expressing neurons in and around the ARH. Contrary to expectations, rats that had sustained lesions of the arcuate nucleus, produced by neonatal monosodium glutamate treatment, displayed a more pronounced suppression (by 25%) of food intake than nonlesioned controls when treated with IL-1 after a 20 hr fast. To confirm and further characterize this unexpected result, a second ablation method was used in a similar paradigm. Animals bearing knife cuts designed to sever major ARH projections displayed an even more accentuated loss of appetite (by 60%, relative to controls) in response to systemic IL-1. This effect exhibited at least some degree of specificity, because the knife cuts did not alter either IL-1 effects on another centrally mediated acute phase response (fever) or the anorexia produced by an alternate agent, fenfluramine. These results fail to support the hypothesized ARH mediation of IL-1-induced anorexia and may suggest rather that the net output of this cell group may serve normally to restrain cytokine-induced reductions in food intake.
Reyes
Teresa M
TM
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies and Foundation for Medical Research, La Jolla, California 92037, USA.
Sawchenko
Paul E
PE
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003714:Denervation; D004435:Eating / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012970:Sodium Glutamate / Q000633:toxicity
D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012970:Sodium Glutamate