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Am J Physiol Regul Integr Comp Physiol 279: R404-R413, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 2, R404-R413, August 2000

Nuclear factor-kappa B inhibitor peptide inhibits spontaneous and interleukin-1beta -induced sleep

Takeshi Kubota, Tetsuya Kushikata, Jidong Fang, and James M. Krueger

Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University College of Veterinary Medicine, Pullman, Washington 99164-6520

Nuclear factor-kappa B (NF-kappa B) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1beta (IL-1beta ), 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 µg for rats, 100 µg 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-µg dose of IP in rats and the 100-µg 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 µg of the IP 12 h before intracerebroventricular injection of IL-1beta (10 ng) significantly attenuated IL-1beta -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.

electroencephalogram; power density; rapid eye movement sleep; rabbits; rats


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