Neuropeptide Y (NPY) increases feeding by direct action in the central nervous system (CNS). Interleukin-1 beta (IL-1 beta), on the other hand, induces anorexia when administered ICV at estimated pathophysiological (e.g., yielded by 1.0 ng/rat dose) and pharmacological (> or = 4.0 ng) concentrations in the cerebrospinal fluid (CSF). In the present study, we investigated NPY/IL-1 beta interactions using the ICV administration. ICV microinfusion of NPY (5.0 micrograms) significantly increased 2-h food intake (by 89%), whereas IL-1 beta decreased 2-h food intake (32% decrease with 1.0 ng/rat; 53% with 4.0 ng/rat; and 51% with 8.0 ng/rat). NPY (5.0 micrograms) blocked the anorexic effect induced by all doses of IL-1 beta when both compounds were administered concomitantly. Central infusion of NPY was also able to induce feeding in IL-1 beta-pretreated rats exhibiting marked anorexia. The results show that ICV-administered NPY blocks and reverses the anorexia induced by estimated pathophysiological and pharmacological concentrations of IL-1 beta in rats. A second interpretation of a data subset is that IL-1 beta attenuates or blocks NPY-induced increase in feeding depending on the IL-1 beta dose used. Blockage and reversal of IL-1 beta-induced anorexia by NPY suggest the importance in studying cytokine-peptide interactions in the regulation of feeding behavior. Understanding these endogenous interactions may produce strategies with potential therapeutic implications for chronic diseases associated with long-term anorexia.