Inactivation of the cerebral NFκB pathway inhibits interleukin-1β-induced sickness behavior and c-Fos expression in various brain nuclei

The behavioral effects of peripherally administered interleukin-1β (IL-1β) 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 NFκB activation, rats were injected into the lateral ventricle of the brain with a specific inhibitor of NFκB activation, the NEMO Binding Domain (NBD) peptide that has been shown previously to abolish completely IL-1β-induced NFκB activation and Cox-2 synthesis in the brain microvasculature. NFκB pathway inactivation significantly blocked the behavioral effects of intraperitoneally administered IL-1β in the form of social withdrawal and decreased food intake, and dramatically reduced IL-1β-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-1β-induced NFκB 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.