Inhibition of tumor necrosis factor in the brain suppresses rabbit sleep

Satoshi Takahashi, Dawn D. Tooley, Levente Kapás, Jidong Fang, Jerome M. Seyer, James M. Krueger

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Tumor necrosis factor (TNF) is a cytokine that possesses many biological activities, including enhancement of non-rapid-eye-movement sleep (NREMS). The role of endogenous TNF in the regulation of spontaneous sleep is unknown. If TNF is involved in sleep regulation, then reduction of endogenous TNF should suppress spontaneous sleep. A soluble TNF-binding protein I (TNF-BP I) and a synthetic fragment of TNF-BP I, TNF-R-(159-178), that contains the biologically active region of TNF-BP I, were used. These substances bind TNF and possess TNF-inhibitory activity; their effects on rabbit sleep after intracerebroventricular injection were determined across a 6-h recording period. Two doses of TNF-BP I (0.05 μg and 0.5 μg) were administered; the higher dose of TNF-BP I significantly decreased NREMS. Four doses of TNF-R-(159-178) (0.25 μg, 2.5 μg, 25 μg and 50 μg) were used. The 25 μg and 50 μg doses significantly suppressed NREMS. The highest dose (50 μg) also decreased REM sleep. These results are consistent with the hypothesis that endogenous brain TNF is involved in the regulation of normal sleep.

Original languageEnglish (US)
Pages (from-to)155-160
Number of pages6
JournalPflügers Archiv European Journal of Physiology
Issue number2
StatePublished - Dec 1995

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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