Somnogenic relationships between tumor necrosis factor and interleukin- 1

Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines. They also induce each other's production and both induce nuclear factor 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 actions. To test this hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sleep deprivation in rabbits. Furthermore, the effects of inhibition of TNF on 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 an IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination of the TNFRF plus the IL- 1RF significantly reduced spontaneous non-rapid eye movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits with the combination of TNFRF and IL-1RF also significantly attenuated sleep rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate physiological sleep.