Interleukin-18 promotes sleep in rabbits and rats.
Interleukin (IL)-1beta is involved in physiological sleep regulation. IL-18 is a member of the IL-1 family, and its signal-transduction mechanism is similar to that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected intracerebroventricularly (icv) into rabbits at the onset of the dark period. The two higher doses of IL-18 markedly increased non-rapid eye movement sleep (NREMS), accompanied by increases in brain temperature (Tbr). These effects were lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during the light period also increased NREMS and Tbr. Similar results were obtained after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal injection of 30 microg/kg of IL-18 slightly, but significantly, increased NREMS, whereas it significantly decreased electroencephalogram slow-wave activity in rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibody significantly attenuated muramyl dipeptide-induced sleep. These data suggest that IL-18 is involved in mechanisms of sleep responses to infection.
Kubota
T
T
College of Veterinary Medicine, Department of VCAPP, Washington State University, Pullman, WA 99164-6520, USA.
Fang
J
J
Brown
R A
RA
Krueger
J M
JM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005334:Fever / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D020382:Interleukin-18 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D008027:Light; D008297:Male; D017440:Photoperiod; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013047:Specific Pathogen-Free Organisms
D000906:Antibodies; D020382:Interleukin-18; D000119:Acetylmuramyl-Alanyl-Isoglutamine