A tumor necrosis factor (TNF) receptor fragment attenuates TNF-alpha- and muramyl dipeptide-induced sleep and fever in rabbits.
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.
Takahashi
S
S
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Kapás
L
L
Krueger
J M
JM
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
D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine