INTERLEUKIN-1 IS INVOLVED IN RESPONSES TO SLEEP-DEPRIVATION IN THE RABBIT

Interleukin-1 (IL-1) is hypothesized to be involved in sleep regulation. Antibodies directed against interleukin-1 beta (anti-IL-1 beta) were injected intracerebroventricularly (ICV) into normal rabbits to determine the effects of the reduction of endogenous IL-1 beta on spontaneous sleep/wake behavior. A 100 mu g dose of anti-IL-1 beta reduced non-rapid eye movements sleep (NREMS) by about 20-min during the first 4-h postinjection without affecting REMS, amplitudes of electroencephalographic (EEG) slow waves, or brain temperature. Plasma concentrations of IL-1 beta, as determined by radioimmunoassay, were detectable in 39 of 79 (49%) blood samples taken before and after 4-h total sleep deprivation (SD). Plasma concentrations of IL-1 beta were, on average, significantly elevated following SD, There was a rebound in NREMS duration and of amplitudes of EEG slow waves of about 2-h duration following SD. This rebound in both parameters was exaggerated if rabbits received vehicle or anti-IL-1 beta in conjunction with SD. However, ICV administration of anti-IL-1 beta at the beginning or end of the SD period attenuated, relative to values obtained after administration of vehicle, the NREMS rebound following SD. It is concluded that SD alters the responsiveness of rabbits to experimental manipulation and that responses to SD in the rabbit are mediated, in part, by IL-1.