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

Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men
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DOI:
10.1016/j.psyneuen.2014.02.020
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发表时间:
2014-06-01
影响因子:
3.7
通讯作者:
Baker, Dewleen G.
Baker, Dewleen G.
中科院分区:
医学2区
文献类型:
--
作者:
Agorastos, Agorastos;Hauger, Richard L.;Baker, Dewleen G.

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背景:白介素6(IL-6)是一种在外周和中枢神经系统(CNS)都具有多效性的细胞因子。IL-6分泌的改变与炎症失调和几种不利的健康后果有关。方法:11名健康男性志愿者在24小时内每小时同时测定血浆和脑脊液中IL-6水平,以表征两室的生理IL-6分泌水平。结果:血浆和脑脊液中IL-6水平在受试者内和脑脊液中均表现出相当大的变异性,血浆和脑脊液中IL-6水平一直较高。脑脊液和血浆IL-6水平均表现出明显的昼夜节律变化,其中脑脊液IL-6水平以24小时为主,血浆IL-6水平呈双相12小时昼夜变化。血浆峰值大约在下午4点。凌晨4点,而脑脊液的高峰期在晚上7点左右。一致的脑脊液和血浆IL-6值之间没有相关性,但有证据表明在负7-8h时有显著的相关性。结论:本研究提供了人类脑脊液中IL-6昼夜节律的证据,并证实了先前观察到的血浆双相昼夜节律模式。我们的结果表明,IL-6在两个隔区的调节不同,并与中枢神经系统局部产生的IL-6一致。讨论了可能的生理意义,并强调了进一步研究的意义。爱思唯尔出版
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