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Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men.

TitleCircadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men.
Publication TypeJournal Article
Year of Publication2014
AuthorsAgorastos, A., Hauger R. L., Barkauskas D. A., Moeller-Bertram T., Clopton P. L., Haji U., Lohr J. B., Geracioti T. D., Patel P. M., Chrousos G. P., & Baker D. G.
Date Published2014 Jun
KeywordsAdult, Circadian Rhythm, Healthy Volunteers, Humans, Interleukin-6, Male, Young Adult

BACKGROUND: Interleukin-6 (IL-6) is a cytokine with pleiotropic actions in both the periphery of the body and the central nervous system (CNS). Altered IL-6 secretion has been associated with inflammatory dysregulation and several adverse health consequences. However, little is known about the physiological circadian characteristics and dynamic inter-correlation between circulating and CNS IL-6 levels in humans, or their significance.METHODS: Simultaneous assessment of plasma and cerebrospinal fluid (CSF) IL-6 levels was performed hourly in 11 healthy male volunteers over 24h, to characterize physiological IL-6 secretion levels in both compartments.RESULTS: IL-6 levels showed considerable within- and between-subject variability in both plasma and CSF, with plasma/CSF ratios revealing consistently higher levels in the CSF. Both CSF and plasma IL-6 levels showed a distinctive circadian variation, with CSF IL-6 levels exhibiting a main 24h, and plasma a biphasic 12h, circadian component. Plasma peaks were roughly at 4 p.m. and 4 a.m., while the CSF peak was at around 7 p.m. There was no correlation between coincident CSF and plasma IL-6 values, but evidence for significant correlations at a negative 7-8h time lag.CONCLUSIONS: This study provides evidence in humans for a circadian IL-6 rhythm in CSF and confirms prior observations reporting a plasma biphasic circadian pattern. Our results indicate differential IL-6 regulation across the two compartments and are consistent with local production of IL-6 in the CNS. Possible physiological significance is discussed and implications for further research are highlighted.

Alternate JournalPsychoneuroendocrinology
PubMed ID24767621


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