Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
J Biol Rhythms. 2013 Aug;28(4):272-7. doi: 10.1177/0748730413494561.
The immune system is regulated by circadian clocks within the brain and immune cells. Environmental circadian disruption (ECD), consisting of a 6-h phase advance of the light:dark cycle once a week for 4 weeks, elevates the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. This indicates that circadian disruption adversely affects immune function; however, it remains unclear how the circadian system regulates this response under ECD conditions. Here, we develop an assay using ex vivo whole-blood LPS challenge to investigate the circadian regulation of immune responses in mice and to determine the effects of ECD on these rhythms. LPS-induced IL-6 release in whole blood was regulated in a circadian manner, peaking during subjective day under both entrained and free-running conditions. This LPS-induced IL-6 release rhythm was associated with daily variation in both white blood cell counts and immune cell responsiveness. ECD increased the overall level of LPS-induced IL-6 release by increasing immune cell responsiveness and not by affecting immune cell number or the circadian regulation of this rhythm. This indicates that ECD produces pathological immune responses by increasing the proinflammatory responses of immune cells. Also, this newly developed whole blood assay can provide a noninvasive longitudinal method to quantify potential health consequences of circadian disruption in humans.
免疫系统受到大脑和免疫细胞内的生物钟的调节。环境昼夜节律紊乱（ECD）由每周一次的光：暗周期提前 6 小时组成，持续 4 周，这会在体内和体外均会引起脂多糖（LPS）的炎症反应升高。这表明昼夜节律紊乱会对免疫功能产生不利影响；然而，目前尚不清楚在 ECD 条件下，生物钟系统如何调节这种反应。在这里，我们使用体外全血 LPS 挑战开发了一种测定方法，以研究昼夜节律对小鼠免疫反应的调节，并确定 ECD 对这些节律的影响。在受约束和自由运行条件下，全血中 LPS 诱导的 IL-6 释放呈昼夜节律调节，在主观白天达到峰值。这种 LPS 诱导的 IL-6 释放节律与白细胞计数和免疫细胞反应性的每日变化相关。ECD 通过增加免疫细胞反应性而不是通过影响免疫细胞数量或这种节律的昼夜调节来增加 LPS 诱导的 IL-6 释放的整体水平。这表明 ECD 通过增加免疫细胞的促炎反应产生病理性免疫反应。此外，这种新开发的全血测定法可以为量化人类昼夜节律紊乱的潜在健康后果提供一种非侵入性的纵向方法。
