IL-6-trans-signalling increases rapid-eye-movement sleep in rats

Interleukin 6 (IL-6), a cytokine of the gp130-signalling-family, plays an important role in immediate immunological functions, in metabolism and in the central nervous system. IL-6-signalling is mediated by classic-signalling via the membrane bound IL-6 receptor or by IL-6-trans-signalling via the soluble IL-6 receptor. Whereas the receptor subunit gp130 is ubiquitously expressed within the body, IL-6 receptor expression is restricted to distinct cell populations. Within the brain parenchyma the IL-6 receptor is sparsely expressed, and therefore the brain is mostly dependent on IL-6-trans-signalling in its response to IL-6. Recently we have shown that IL-6-trans-signalling but not classic-signalling plays a pivotal role in the establishment and maintenance of chronic inflammation and cancer, whereas its role in sleep regulation has not been studied so far. We reasoned that the IL-6-trans-signalling mimetic Hyper-IL-6 which in contrast to IL-6 alone can activate almost all cells of the brain might have a profound effect on sleep regulation and performed sleep recordings with rats injected with recombinant Hyper-IL-6. In the present study, the i.c.v. administration of the designer cytokine Hyper-IL-6 into rats at dark onset increased the amount of rapid-eye-movement sleep (REM sleep) but did not affect non-rapid-eye-movement sleep (non-REM sleep). Our data define a new role of IL-6-trans-signalling in sleep regulation.