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 mu l icv; 2) 27 degrees C T-amb with PFS, intracerebroventricularly; and 3) 27 degrees C T-amb with the TNF-RF, 50 mu g icv. 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 Ta-mb 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.