Interleukin-4 inhibits spontaneous sleep in rabbits.
Proinflammatory cytokines, including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha, are involved in sleep regulation. IL-4 is an antiinflammatory cytokine that inhibits proinflammatory cytokine production. The hypothesis that IL-4 should attenuate sleep was studied by determining the effects of IL-4 on rabbit spontaneous sleep. Thirty-six rabbits were used. Four doses of IL-4 (0.25, 2.5, 25, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-4 (25 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were done in the same rabbits on different days. The three highest doses of IL-4 significantly inhibited spontaneous non-rapid eye movement sleep if IL-4 was given during the light cycle. The highest dose of IL-4 (250 ng) also significantly decreased rapid eye movement sleep. On the other hand, IL-4 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-4 provide additional evidence for the hypothesis that a brain cytokine network is involved in the regulation of physiological sleep.
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington 99164, USA.
T
T
Kushikata
J
J
Fang
Y
Y
Wang
J M
JM
Krueger
D000513:Alpha Rhythm / Q000187:drug effects; D000818:Animals; D001611:Beta Rhythm / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D004569:Electroencephalography / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D007276:Injections, Intraventricular; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D008027:Light; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013826:Theta Rhythm / Q000187:drug effects
D011994:Recombinant Proteins; D015847:Interleukin-4