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The Journal of Neuroscience, June 15, 2002, 22(12):5091-5099

Involvement of the Arcuate Nucleus of the Hypothalamus in Interleukin-1-Induced Anorexia

Teresa M. Reyes and Paul E. Sawchenko

Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies and Foundation for Medical Research, La Jolla, California 92037

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 µg/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.

Key words: anorexia; arcuate nucleus; interleukin-1; neuropeptide Y; proopiomelanocortin; sickness behavior

Copyright © 2002 Society for Neuroscience  0270-6474/02/22125091-09$05.00/0


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