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Oyanedel, C.N.* ; Kelemen, E. ; Scheller, J.* ; Born, J. ; Rose-John, S.*

Peripheral and central blockade of interleukin-6 trans-signaling differentially affects sleep architecture.

Brain Behav. Immun. 50, 178-185 (2015)
Postprint DOI PMC
Open Access Green
The immune system is known to essentially contribute to the regulation of sleep. Whereas research in this regard focused on the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor, the role of interleukin-6 (IL-6) in sleep regulation has been less intensely studied, probably due to the so far seemingly ambiguous results. Yet, this picture might simply reflect that the effects of IL-6 are conveyed via two different pathways (with possibly different actions), i.e., in addition to the 'classical' signaling pathway via the membrane bound IL-6 receptor (IL-6R), IL-6 stimulates cells through the alternative 'trans-signaling' pathway via the soluble IL-6R. Here, we concentrated on the contributions of the trans-signaling pathway to sleep regulation. To characterize this contribution, we compared the effect of blocking IL-6 trans-signaling (by the soluble gp130Fc fusion protein) in the brain versus body periphery. Thus, we compared sleep in transgenic mice expressing the soluble gp130Fc protein only in the brain (GFAP mice) or in the body periphery (PEPCK mice), and in wild type mice (WT) during a 24-h period of undisturbed conditions and during 18h following a 6-h period of sleep deprivation. Compared with WT mice, PEPCK mice displayed less sleep, particularly during the late light phase, and this was accompanied by decreases in slow wave sleep (SWS) and rapid eye movement (REM) sleep. Following sleep deprivation PEPCK mice primarily recovered REM sleep rather than SWS. GFAP mice showed a slight decrease in REM sleep in combination with a profound and persistent increase in EEG theta activity. In conclusion, peripheral and central nervous IL-6 trans-signaling differentially influences brain activity. Peripheral IL-6 trans-signaling appears to more profoundly contribute to sleep regulation, mainly by supporting SWS.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Il-6 Trans-signaling ; Rem Sleep ; Sleep ; Slow Wave Activity ; Slow Wave Sleep ; Theta Rhythm
ISSN (print) / ISBN 0889-1591
e-ISSN 1090-2139
Zeitschrift Brain, Behavior and Immunity
Quellenangaben Band: 50, Heft: , Seiten: 178-185 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)