MICE LACKING THE TNF 55 KDA RECEPTOR FAIL TO SLEEP MORE AFTER TNF-ALPHA TREATMENT

Tumor necrosis factor (TNF) is a well characterized sleep-regulatory s ubstance. To study receptor mechanisms for the sleep-promoting effects of TNF, sleep patterns were determined in control and TNF 55 kDa rece ptor knock-out (TNFR-KO) mice with a B6 x 129 background after intrape ritoneal injections of saline or murine TNF alpha. The TNFR-KO mice ha d significantly less baseline sleep than the controls. TNF alpha dose- dependently increased non-rapid eye movement sleep (NREMS) in the cont rols but did not influence sleep in TNFR-KO mice. Although TNFR-KO mic e failed to respond to TNF alpha, they had an increase in NREMS and a decrease in rapid eye movement sleep after interleukin-1 beta treatmen t. These results indicate that TNF alpha affects sleep via the 55 kDa receptor and provide further evidence that TNF alpha is involved in ph ysiological sleep regulation. Current results also extend the list of species to mice in which TNF alpha and interleukin-1 beta are somnogen ic.