Central nervous system IL-1 beta system and neuropeptide Y mRNAs during IL-1 beta-induced anorexia in rats

Interleukin-1 beta (IL-1 beta) induces anorexia and neuropeptide Y (NPY) increases feeding by direct action in the central nervous system (CNS). IL-1 beta, depending on the dose, attenuates or blocks NPY-induced feeding. This suggests that IL-1 beta-NPY interactions may be involved in IL-1 beta-induced anorexia. Here, RNase protection assays were used to investigate the effects of the chronic intracerebroventricular (ICV) administration of IL-1 beta (at a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid) on mRNA levels of IL-1 beta system components and NPY in the cerebellum, parietofrontal cortex, hippocampus, hypothalamus, and midbrain. The results show that the chronic ICV administration of IL-1 beta (8.0 ng/24 h for 72 h) differentially induced IL-1 beta system components across brain regions in anorectic rats. IL-1 beta mRNA and IL-1 receptor antagonist (IL-1Ra) mRNA were induced similarly, exhibiting highest and lowest expression 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 hypothalamus and cerebellum. NPY mRNA expression showed a small, but significant decrease in the hypothalamus. Heat-inactivated IL-1 beta (8.0 ng/24 h for 72 h) had no effect on the behavioral or molecular profiles. The results suggest that endogenous upregulation of IL-1 beta contributes to IL-1 beta-induced anorexia, and that modification of NPY mechanisms also may be involved.