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Figure 2. Proposed mechanism of action. Effects of sleep and circadian rhythm on IL-6 signaling in humans are separated. Sleep strikingly increases sIL-6R plasma concentrations, especially in the late night sleep with predominant rapid eye movement (REM) sleep. Slow wave sleep (SWS) is predominant during the early part of sleep and is associated with a concomitant increase in growth hormone (GH) which counteracts this process. Sleep-induced stimulation of sIL-6R expression first promotes liberation of the PC-sIL-6R variant peaking in the morning after awakening (8:00 h), and is subsequently followed (
6 hours later) by an increase in DC-sIL-6R. In contrast to sIL-6R concentrations, nocturnal increases in mIL-6R expression and IL-6 production do not depend on sleep but are caused by a circadian oscillation. Thus sleep, via enhancing sIL-6R promotes IL-6 trans-signaling and facilitates an integrated influence on multiple organ systems.
