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: 6819444
• 负责人: Benjamin Natelson
• 金额: $ 33.49万
• 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/6819444
• 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.

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，但没有确切的数据支持免疫假说。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宁静/不安睡眠中的作用。许多CFS患者的睡眠受到干扰，我们认为这是由于一些患者的睡眠干扰和睡眠产生细胞因子的模式异常所致。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-血浆水平的ELISA，外周血单核细胞（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CFS患者的数据与健康对照者的数据进行比较，在血液采样的夜晚，他们的总睡眠时间与CFS患者相匹配。由于一些CFS患者的睡眠没有中断，我们开发了一个2x2的设计：CFS与对照组;睡眠干扰与正常睡眠。这种设计将使我们能够确定CFS这种疾病，而不是睡眠障碍，这种疾病的症状，是否是细胞因子模式改变的原因。我们将在受试者进行最大运动量测试后，在一个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症状的运动会使已经失调的细胞因子睡眠网络恶化，而睡眠剥夺也会通过增加没有睡眠问题的CFS患者和对照组中的睡眠产生细胞因子而放大差异，但不会在睡眠中断的患者中。