Sleep and Cytokines in Chronic Fatigue Syndrome

慢性疲劳综合征是一种医学上无法解释的疾病。其原因的主要假设之一是免疫功能障碍。然而，没有确切的数据支持免疫学假说。这可能是因为之前的研究人员忽略了细胞因子在产生宁静睡眠中的作用。许多CFS患者的睡眠受到干扰，这可能是因为一些患者的睡眠干扰细胞因子网络上调。我们建议测量睡眠干扰细胞因子（即，IL-4和IL-10）和产生睡眠的细胞因子（IL-1 β和TNF-α）在CFS患者的第二个晚上在睡眠实验室（第一个晚上进行处理众所周知的“第一夜效应”，并消除原发性睡眠障碍或无法入睡的患者与仪器）。在进行这些研究时，我们意识到没有“金标准”来量化细胞因子，因此我们将使用三种不同的方法-血浆中的ELISA、来自外周血单核细胞（PBM）的基因信息和ELISPOT来评估PBM对免疫探针的功能。我们之所以研究女性，是因为CFS主要是一种女性疾病，因为我们想排除主要发生在男性身上的原发性睡眠障碍受试者，因为女性的细胞因子水平明显高于男性。我们将CFS患者的数据与健康对照组的数据进行比较，健康对照组与CFS患者一样疲劳，因为我们将在采血前一晚剥夺他们的睡眠。此外，在血液采样的夜晚，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患者的睡眠没有中断，因此该设计将提供睡眠没有中断的健康受试者和睡眠与睡眠中断的CFS患者相同量的健康受试者。最后，我们将在一天后重复整个方案，其中受试者进行最大运动试验，因为众所周知的疲劳加重CFS。我们预计，运动会使一些CFS患者的睡眠比平时更差，并加剧已经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.