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

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

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Nuclear factor-κB (NF-κB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1β (IL-1β), tumor necrosis factor-α, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-κB activation would attenuate sleep. A NF-κB 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-1β (10 ng) significantly attenuated IL-1β-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-κB is a crucial factor in physiological sleep regulation.

Original languageEnglish (US)
Pages (from-to)R404-R413
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2 48-2
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)


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