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.
Takahashi
S
S
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University College of Veterinary Medicine, Pullman, Washington 99164-6520, USA.
Kapás
L
L
Fang
J
J
Krueger
J M
JM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000737:chemistry; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012892:Sleep Deprivation / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D010446:Peptide Fragments; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha