Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cyto
kines. They also induce each other's production and both induce nuclear fac
tor kappa B activation, which in turn enhances IL-1 and TNF transcription.
We hypothesized that TNF and IL-1 could influence each other's somnogenic a
ctions. To test this hypothesis, we determined the effects of blocking bath
endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sl
eep deprivation in rabbits. Furthermore, the effects of inhibition of TNF o
n IL-1-induced sleep and the effects of blocking IL-1 on TNF-induced sleep
were determined. A TNF receptor fragment (TNFRF), as a TNF inhibitor, and a
n IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intrace
rebroventricular injection of a combination of the TNFRF plus the IL-1RF si
gnificantly reduced spontaneous non-rapid eye movement sleep by 87 min over
a 22-h recording period. Pretreatment of rabbits with the combination of T
NFRF and IL-1RF also significantly attenuated sleep rebound after sleep dep
rivation. Furthermore, the TNFRF significantly attenuated IL-1-induced slee
p but not fever. Finally, the IL-1RF blacked TNF-induced sleep responses bu
t not fever. Results indicate that TNF and IL-1 cooperate to regulate physi
ological sleep.