CENTRAL-NERVOUS-SYSTEM IL-1-BETA SYSTEM AND NEUROPEPTIDE-Y MESSENGER-RNAS DURING IL-1-BETA-INDUCED ANOREXIA IN RATS

Interleukin-1 beta (IL-1 beta) induces anorexia and neuropeptide Y (NP Y) increases feeding by direct action in the central nervous system (C NS). IL-1 beta, depending on the dose, attenuates or blocks NPY-induce d feeding. This suggests that IL-1 beta-NPY interactions may be involv ed in IL-1 beta-induced anorexia. Here, RNase protection assays were u sed to investigate the effects of the chronic intracerebroventricular (ICV) administration of IL-1 beta (at a dose that yields estimated pat hophysiological concentrations in the cerebrospinal fluid) on mRNA lev els of IL-1 beta system components and NPY in the cerebellum, parietof rontal cortex, hippocampus, hypothalamus, and midbrain. The results sh ow that the chronic ICV administration of IL-1 beta (8.0 ng/24 h for 7 2 h) differentially induced IL-1 beta system components across brain r egions in anorectic rats. IL-1 beta mRNA and IL-1 receptor antagonist (IL-1Ra) mRNA were induced similarly, exhibiting highest and lowest ex pression levels in the hypothalamus and hippocampus, respectively. IL- 1 receptor type I (IL-1RI) mRNA and the soluble form of IL-1 receptor accessory protein (IL-1R AcP II) mRNA were also induced in the hypotha lamus and cerebellum. NPY mRNA expression showed a small, but signific ant decrease in the hypothalamus. Heat-inactivated IL-1 beta (8.0 ng/2 4 h for 72 h) had no effect on the behavioral or molecular profiles. T he results suggest that endogenous upregulation of IL-1 beta contribut es to IL-1 beta-induced anorexia, and that modification of NPY mechani sms also may be involved. (C) 1997 Elsevier Science Inc.