title: Sleep enhances IL-6 trans-signaling in humans.
abstract: Sleep is commonly considered to support immune defense. The underlying sleep-immune interaction appears to rely critically on cytokines, like interleukin-6 (IL-6), that combine effects on immune and neuronal functions. The IL-6 signal is conveyed in two ways: it stimulates a restricted group of (mostly immune) cells via membrane-bound IL-6 receptors (mIL-6R) by forming a complex with soluble IL-6R (sIL-6R), and it stimulates (via membrane-bound gp130) a great variety of other cell types--a process termed trans-signaling. Focusing on the receptor side of IL-6 signaling, we examined the effect of sleep on sIL-6R plasma concentrations, mIL-6R expression, plasma sgp130, and numbers of IL-6-producing monocytes in healthy humans who were tested during a regular sleep-wake cycle and 24 h of wakefulness while blood was sampled repeatedly. Sleep strongly enhanced concentrations of sIL-6R, exceeding wake levels by 70% at the end of sleep. This rise was due to an increase in the PC (proteolytic cleavage) rather than the DS (differentially spliced) variant of sIL-6R. Sleep did not affect IL-6-producing monocytes, mIL-6R density, or sgp130 concentrations. The selective increase in sIL-6R implicates an enhanced trans-signaling capacity whereby sleep distinctly widens the profile of IL-6 actions, enabling an integrated influence on brain and peripheral organs.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23a, Lübeck 23538, Germany.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Dimitrov
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.forename: Mari A
authors.initials: MA
authors.lastname: Nowell
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Jan
authors.initials: J
authors.lastname: Born
mesh_terms: D000328:Adult; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D008297:Male; D009000:Monocytes; D019947:Receptors, Interleukin-6 / Q000097:blood* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D012890:Sleep / Q000276:immunology*; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D019947:Receptors, Interleukin-6