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。其原因的主要假说之一是免疫功能障碍，但没有确凿的数据支持这一免疫学假说。我们认为这是因为之前的研究人员忽略了细胞因子在产生安宁/不安睡眠中的作用。许多CFS患者有睡眠障碍，我们推测这是由于一些患者睡眠障碍和睡眠产生细胞因子的模式异常所致。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)。在进行这些研究时，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--血浆水平的ELISA、外周血单个核细胞(PBMC)中的基因信息和ELISPOT来评估PBMC对免疫探针的反应。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。我们将排除患有抑郁症的女性，因为抑郁症会改变睡眠和细胞因子。我们将比较CFS患者和健康对照组的数据，在采血之夜，他们的总睡眠时间将与CFS患者匹配。由于一些CFS患者睡眠不受干扰，我们开发了一个2x2设计：CFS与对照组；睡眠障碍与正常睡眠。这一设计将允许我们确定CFS疾病，而不是睡眠障碍，这是疾病的一种症状，是否导致细胞因子模式改变。我们将在受试者进行最大运动测试后和完全睡眠剥夺的夜晚重复整个方案。我们预计，已知会加剧CFS症状的运动将恶化本已失调的细胞因子睡眠网络，而睡眠剥夺也将通过增加没有睡眠问题的CFS患者和对照组(但不包括睡眠中断的患者)中产生睡眠的细胞因子来放大这种差异。

DESCRIPTION: Chronic fatigue syndrome is a medically unexplained illness. One of the major hypotheses for its cause is immunological dysfunction, but no firm data exist to support the immunological hypothesis. We believe this is because prior researchers have ignored the role of cytokines in producing restful/restless sleep. Many CFS patients have disrupted sleep, and we posit that this occurs because of abnormalities in the pattern of sleep disrupting and sleep producing 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 of plasma levels, gene message in peripheral blood mononuclear cells (PBMC) and ELISPOT to assess PBMC responses 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 that occur mostly in men, and because women have substantially higher levels of cytokines than men. We will exclude women with depression because depression alters sleep and cytokines. We will compare data of CFS patients to those of healthy controls who, on the blood sampling night, will have their total sleep time matched to CFS patients. Since some CFS patients sleep without disruption, we have developed a 2x2 design: CFS vs controls; and sleep disturbed vs normally sleeping. This design will allow us to determine whether CFS, the illness, rather than the disturbed sleep, a symptom of the illness, is responsible for altered cytokine patterns. We will repeat this entire protocol after subjects perform a maximal exercise test and during a night of total sleep deprivation. We anticipate that exercise, which is known to exacerbate CFS symptoms, will worsen an already dysregulated cytokine sleep network while sleep deprivation will also magnify the differences by increasing sleep-producing cytokines in CFS patients without sleep problems and in controls but not in patients with disrupted sleep.