Inhibition of tumor necrosis factor prevents warming-induced sleep responses in rabbits

Tumor necrosis factor (TNF) is a key regulatory component of sleep. In the present study, we determined the effects of intracerebroventricular injection of a TNF inhibitor, a soluble TNF receptor fragment (TNF-RF), on sleep responses of rabbits during and after exposure to mild increases in ambient temperature (T(amb)). Each rabbit (n = 8) was recorded under three conditions: 1) normal T(amb) (21 degrees C) with pyrogen-free saline (PFS), 50 microl i.c.v.; 2) 27 degrees C T(amb) with PFS, intracerebroventricularly; and 3) 27 degrees C T(amb) with the TNF-RF, 50 microg i.c.v. When T(amb) was increased to 27 degrees C from 21 degrees C, it was kept at that temperature for 6 h after injection. The higher T(amb) alone significantly increased non-rapid eye movement sleep, decreased rapid eye movement sleep, and increased brain temperature (T(br)) across the 23-h recording period. Electroencephalogram slow-wave activity was also significantly enhanced during the 6-h warming period. In contrast, all of the sleep responses associated with the higher T(amb) were absent if rabbits were pretreated with the TNF-RF. The elevated T(br) during the higher T(amb) was not affected by the TNF-RF. The present results suggest that brain TNF is involved in the mild increases in T(amb)-induced sleep responses.