title: A tumor necrosis factor (TNF) receptor fragment attenuates TNF-alpha- and muramyl dipeptide-induced sleep and fever in rabbits.
abstract: It is hypothesized that tumour necrosis factor (TNF) is an endogenous substance involved in sleep responses occurring during bacterial infection. If this hypothesis is correct, then blocking endogenous TNF, using a TNF inhibitor, should attenuate the bacterial cell wall-derived, muramyl dipeptide (MDP)-induced sleep. To test this hypothesis, the effects of intracerebroventricular (i.c.v.) injection of a TNF inhibitor, a biologically active fragment of the soluble TNF 55 kDa receptor (TNFRF), on TNF-alpha- and MDP-induced sleep were determined in rabbits. I.c.v. injection of 250 ng human recombinant TNF-alpha- or 150 pmol MDP increased non-rapid-eye-movement sleep (NREMS), decreased rapid-eye-movement sleep (REMS), enhanced electroencephalogram slow-wave activity (SWA) during NREMS and induced fever. Pretreatment of rabbits with 25 micrograms of the TNFRF significantly inhibited TNF-alpha- and MDP-induced sleep and fever responses. Finally, intravenously (i.v.) injected MDP enhanced NREMS, suppressed REMS, enhanced SWA, and induced fever; pretreatment of animals with the TNFRF injected centrally attenuated i.v. MDP-induced sleep responses but not fever. These results suggest that the TNFRF acts as a TNF-alpha antagonist in vivo and support the hypothesis that MDP-induced sleep is partially mediated via brain TNF-alpha.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: L
authors.initials: L
authors.lastname: Kapás
authors.forename: J M
authors.initials: JM
authors.lastname: Krueger
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D008297:Male; D011817:Rabbits; D012895:Sleep, REM / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine