Vgontzas A N, Bixler E O, Lin H-M, Prolo P, Trakada G, Chrousos G P
Sleep Research and Treatment Center, Department of Psychiatry, Penn State College of Medicine, Hershey, PA 17033, USA.
Neuroimmunomodulation. 2005;12(3):131-40. doi: 10.1159/000084844.
Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative 'sleep factor' and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of 'detrended' data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.
白细胞介素-6（IL-6）是一种由多种免疫细胞和非免疫细胞产生的多效性细胞因子，参与人体许多病理生理机制。许多研究表明，IL-6是一种假定的“睡眠因子”，其昼夜分泌与睡眠/嗜睡相关。在发作性睡病和阻塞性睡眠呼吸暂停等白天过度嗜睡的疾病中，IL-6水平会升高。它与体重指数呈正相关，可能是肥胖中嗜睡的介导因子。此外，这种细胞因子的分泌会受到急性或部分短期睡眠总剥夺的刺激，这反映了睡眠剥夺个体所经历的嗜睡增加。评估健康年轻成年人中IL-6的24小时分泌模式的研究表明，IL-6以双相昼夜模式分泌，在大约08:00和21:00有两个最低点，在大约19:00和05:00有两个最高点。相比之下，在睡眠剥夺后或睡眠障碍（如失眠）中，IL-6在白天达到峰值，并根据应激系统活动水平（即皮质醇分泌），导致嗜睡和深度睡眠（皮质醇水平低）或疲劳感和睡眠质量差（皮质醇水平高）。为了解决对24小时采血实验开始和结束时IL-6水平差异潜在影响的担忧，我们对年轻和老年健康个体的“去趋势”数据进行了余弦分析。这项新分析并未影响年轻成年人中IL-6分泌的双相昼夜模式，而在老年个体中，昼夜模式变平，差异更大，该分析增强了这种模式变化。最后，IL-6在大鼠中似乎具有促睡眠作用，并表现出与这些动物的睡眠/觉醒周期一致的昼夜节律。我们得出结论，IL-6是嗜睡的介导因子，其昼夜模式反映了睡眠的稳态驱动力。
