Sleep and Cytokines in Chronic Fatigue Syndrome

慢性疲劳综合症中的睡眠和细胞因子

• 批准号: 7067678
• 负责人: Benjamin Natelson
• 金额: $ 62.74万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067678
• 关键词: chronic disease /disorder; chronic fatigue syndrome; clinical research; cytokine; disease /disorder etiology; enzyme linked immunosorbent assay; exercise; female; gene expression; gene expression profiling; genetic regulation; human genetic material tag; human subject; immunogenetics; immunopathology; immunoregulation; interleukin 1; interleukin 10; interleukin 4; patient oriented research; polysomnography; sleep; tumor necrosis factor alpha; women' s health

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.

描述：慢性疲劳综合症是一种医学上无法解释的疾病。其原因的主要假设之一是免疫功能障碍，但没有可靠的数据支持该免疫学假设。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/不安的睡眠中的作用。许多慢性疲劳综合症患者的睡眠受到干扰，我们推测这是由于某些患者睡眠干扰模式和睡眠产生细胞因子的异常所致。我们建议在睡眠实验室的第二天晚上测量 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-1beta 和 TNF-α）（第一晚是为了应对具有众所周知的“首夜效应”，并消除患有原发性睡眠障碍或无法使用仪器入睡的患者）。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 ELISA、外周血单核细胞 (PBMC) 中的基因信息和 ELISPOT 来评估 PBMC 反应到免疫学探针。我们之所以研究女性，是因为慢性疲劳综合症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，并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 患者的数据与健康对照者的数据，健康对照者在采血之夜的总睡眠时间将与 CFS 患者相匹配。由于一些 CFS 患者睡眠不受干扰，我们开发了 2x2 设计：CFS 与对照组；睡眠受到干扰与正常睡眠相比。这种设计将使我们能够确定慢性疲劳综合症（CFS）这种疾病，而不是睡眠障碍（疾病的症状），是否导致了细胞因子模式的改变。在受试者进行最大运动测试后以及在完全睡眠剥夺的夜晚期间，我们将重复整个协议。我们预计，众所周知，运动会加剧慢性疲劳综合症症状，从而使本来就失调的细胞因子睡眠网络变得更加恶化，而睡眠不足也会通过增加无睡眠问题的慢性疲劳综合症患者和对照组的睡眠产生细胞因子来放大这种差异，但在睡眠问题的患者中则不会。睡觉。