Effect of interleukin-1 beta on EEG power density during sleep depends on circadian phase

The cytokine interleukin (IL)-1 is a key mediator of the somnogenic response to immune challenge. In this vehicle-controlled study we evaluated circadian interference with the sleep-promoting effects of IL-1 beta. In two randomized experiments, rats mere injected intracerebroventricularly with 5 ng IL-1 beta either at the beginning of the rest phase or at the beginning of the activity phase. Recordings were made during the 24 h preceding the injections (baseline) and during the first 12 postinjection hours. To avoid masking effects of light, the rats were maintained under a skeleton photoperiod during recording. During both the rest and activity phase, IL-1 beta induced fever and initially promoted non-rapid eye movement sleep (non-REMS) and suppressed rapid eye movement sleep (REMS). The effect of IL-1 beta on the duration of non-REMS and electroencephalogram (EEG) power densities within non-REMS was related to circadian phase. During the rest phase, IL-1 beta resulted in a minor increase in non-REMS duration but a prominent enhancement in EEG activity in the delta (0.5-4 Hz) and most other frequency bands. During the activity phase, IL-1 beta evoked a larger increase in the duration of non-REMS but hardly affected EEG activity within this state. Thus the effects of IL-1 beta on non-REMS are strongly influenced by diurnal phase. The alterations in EEG power density are in contrast to those elicited by sleep deprivation, which are largely independent of time of day. It is concluded that IL-1 beta activates EEG regulatory mechanisms mediated by processes that depend on circadian phase.