期刊
PSYCHONEUROENDOCRINOLOGY
卷 44, 期 -, 页码 71-82出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2014.02.020
关键词
Interleukin-6 (IL-6); Cytokines; Circadian; Immune; Inflammation; Blood brain-barrier (BBB); Cerebrospinal fluid (CSF); Sleep; Stress; Neuroimmunology
资金
- VA CSR&D Program, MERIT
- VA Center of Excellence for Stress and Mental Health San Diego, CA, USA
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 24 h, 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 24 h, and plasma a biphasic 12 h, 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 7-8 h 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. Published by Elsevier
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