Inactivation of the Cerebral NFκB Pathway Inhibits Interleukin-1β-Induced Sickness Behavior and c-Fos Expression in Various Brain Nuclei

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Abstract
The behavioral effects of peripherally administered interleukin-1 (IL-1) are mediated by the production of cytokines and other proinflammatory mediators at the level of the blood–brain interface and by activation of neural pathway. To assess whether this action is mediated by NFB activation, rats were injected into the lateral ventricle of the brain with a specific inhibitor of NFB activation, the NEMO Binding Domain (NBD) peptide that has been shown previously to abolish completely IL-1-induced NFB activation and Cox-2 synthesis in the brain microvasculature. NFB pathway inactivation significantly blocked the behavioral effects of intraperitoneally administered IL-1 in the form of social withdrawal and decreased food intake, and dramatically reduced IL-1-induced c-Fos expression in various brain regions as paraventricular nucleus, supraoptic nucleus, and lateral part of the central amygdala. These findings strongly support the hypothesis that IL-1-induced NFB activation at the blood–brain interface is a crucial step in the transmission of immune signals from the periphery to the brain that underlies further events responsible of sickness behavior.