Nuclear factor-kappaB inhibitor peptide inhibits spontaneous and interleukin-1beta-induced sleep.
Nuclear factor-kappaB (NF-kappaB) 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-kappaB activation would attenuate sleep. A NF-kappaB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 microg for rats, 100 microg 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-microg dose of IP in rats and the 100-microg 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 microg 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-kappaB is a crucial factor in physiological sleep regulation.
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University College of Veterinary Medicine, Pullman 99164-6520, USA.
T
T
Kubota
T
T
Kushikata
J
J
Fang
J M
JM
Krueger
D000818:Animals; D005334:Fever / Q000503:physiopathology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D017440:Photoperiod; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D013997:Time Factors
D007375:Interleukin-1; D016328:NF-kappa B; D010455:Peptides