Nuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep

Nuclear factor-kappa B (NF-kappa B) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-kappa B activation would attenuate sleep. A NF-kappa B cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 mg for rats, 100 mu g for rabbits). On a separate day, time-matched control injections of a cell-permeable inactive control peptide were done in the same animals. The 50-mu g dose of IP in rats and the 100-mu g dose in rabbits significantly inhibited non-rapid eye movement sleep and rapid eye movement sleep if administered during the light period. Moreover, pretreatment of rabbits with 100 mg of the IP 12 h before intracerebroventricular injection of IL-1 beta (10 ng) significantly attenuated IL-1 beta-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-kappa B is a crucial factor in physiological sleep regulation.