Sleep and Cytokines in Chronic Fatigue Syndrome

描述：慢性疲劳综合症是一种医学上无法解释的疾病。对其原因的主要假设之一是免疫功能障碍。然而，目前还没有确凿的数据来支持免疫学假说。这很可能是因为之前的研究人员忽略了细胞因子在产生安宁睡眠中的作用。许多CFS患者睡眠中断，这可能是由于一些患者睡眠中断细胞因子的上调网络造成的。我们建议在睡眠实验室的第二个晚上(第一个晚上是为了处理众所周知的“第一夜效应”，并通过仪器消除患有原发性睡眠障碍或无法入睡的患者)测量CFS患者的睡眠干扰细胞因子(即IL-4和IL-10)和睡眠产生细胞因子(IL-1β和TNF-α)。在这些研究中，我们意识到没有量化细胞因子的“金标准”，因此我们将使用三种不同的方法-血浆中的ELISA法、外周血单核细胞(PBM)的基因信息和ELISPOT来评估PBM的免疫探针功能。我们之所以会研究女性，只是因为CFS主要是女性的一种疾病，因为我们想要排除患有主要发生在男性的原发性睡眠障碍的受试者，而且因为女性的细胞因子水平比男性高得多。我们会将CFS患者的数据与健康对照组的数据进行比较，后者会像CFS患者一样疲惫，因为我们会在采血前一晚剥夺他们的睡眠。此外，在采血之夜，我们建议将对照组与CFS患者的总睡眠时间相匹配。由于一些CFS患者睡眠不受干扰，这一设计将为健康受试者提供不受干扰的睡眠，并为健康受试者提供与睡眠中断患者相同的睡眠时间。最后，我们将在受试者进行最大运动测试的一天后重复整个方案，因为众所周知，CFS因劳累而恶化。我们预计，运动将使一些CFS患者的睡眠状况比平时更差，并加剧本已失调的细胞因子睡眠网络。

DESCRIPTION: Chronic fatigue syndrome is a medically unexplained illness. One of the major hypotheses for its cause is immunological dysfunction. Nevertheless, no firm data exist to support the immunological hypothesis. This is likely because prior researchers have ignored the role of cytokines in producing restful sleep. Many CFS patients have disrupted sleep, and it is possible that this occurs because of an upregulated network of sleep disrupting cytokines in some patients. We propose to measure sleep disrupting cytokines (i.e., IL-4 and IL-10) and sleep producing cytokines (IL-1beta and TNF-alpha) in CFS patients on their second night in the sleep laboratory (the first night being done to deal with the well known "first night effect" and to eliminate patients with primary sleep disorders or an inability to sleep with instrumentation). In doing these studies, we are aware that there is no "gold standard" to quantify cytokines, and so we will use three different approaches - ELISA in plasma, gene message from peripheral blood monocytes (PBM) and ELISPOT to assess PBM function to immunological probes. We will study women only because CFS is predominantly an illness of women, because we want to exclude subjects with primary sleep disorders, which occur mostly in men, and because women have substantially higher levels of cytokines than men. We will compare data of CFS patients to those of healthy controls who will be as fatigued as the CFS patients because we will sleep deprive them on the night before the blood sampling night. Moreover, on the blood sampling night, we propose to match the controls to CFS patients for total sleep time. Since some CFS patients sleep without disruption, this design will provide healthy subjects sleeping without disruption and healthy subjects who sleep the same amount as those CFS patients with disrupted sleep. Finally, we will repeat this entire protocol after a day in which subjects perform a maximal exercise test because of the well-known exacerbation of CFS by exertion. We are anticipating that exercise will make some CFS patients sleep even worse than usual and exacerbate an already dysregulated cytokine sleep network.