Interleukin-6 alters sleep of rats

Although it is well established that the cytokines tumor necrosis factor (TNF) and interleukin (IL)-1 regulate sleep, there is no direct evidence implicating IL-6 in the regulation/modulation of sleep. We tested the hypotheses that central administration of rat recombinant IL-6 increases non-rapid eye movements (NREM) sleep of rats, and that central administration of anti-IL-6 antibodies reduces NREM sleep. Effective doses of IL-6 (100 and 500 ng) initially enhance NREM sleep, after which NREM sleep may be suppressed. IL-6 induces febrile responses at doses lower (50 ng) than those required to alter sleep. Rapid eye movements (REM) sleep is not altered by the doses of IL-6 tested. Central administration of monoclonal or polyclonal anti-rat IL-6 antibodies does not alter any of the parameters determined in this study. Collectively, these results support the hypothesis that IL-6 possesses sleep modulatory properties. However, this cytokine may not be involved in the regulation of spontaneous sleep in healthy animals because antagonizing the IL-6 system using antibodies does not alter sleep. The interpretation of these data is consistent with those of previous studies demonstrating correlations between increased IL-6 and excessive daytime sleepiness during some pathophysiological conditions.