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：慢性疲劳综合征是一种医学上无法解释的疾病。免疫功能障碍是其原因的主要假设之一，但没有牢固的数据来支持免疫学假设。我们认为这是因为先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患者的睡眠破坏了，我们认为这是由于某些患者的睡眠破坏和睡眠产生细胞因子的异常而发生的。我们建议在CFS患者的第二个晚上在睡眠实验室的第二个晚上（第一个晚上，与众所周知的“第一个夜晚的效果”处理“第一个夜晚的效果”，并消除具有初级睡眠障碍的患者或消除具有仪器的患者，请在CFS患者中测量破坏细胞因子（即IL-4和IL-10）并产生睡眠的细胞因子（IL-1Beta和TNF-Alpha）的睡眠。在进行这些研究时，我们知道没有“黄金标准”可以量化细胞因子，因此我们将使用三种不同的方法 - 血浆水平的ELISA，外周血单核细胞中的基因信息（PBMC）和ELISPOT来评估对免疫学探针的PBMC反应。我们之所以研究女性，是因为CFS是女性的疾病，因为我们想排除主要发生在男性中的原发性睡眠障碍的受试者，并且女性的细胞因子水平高于男性。我们将排除患有抑郁症的妇女，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的患者的数据，他们在血液采样之夜将与CFS患者的总睡眠时间匹配。由于某些CFS患者不受破坏而入睡，因此我们开发了2x2的设计：CFS与控件；睡眠打扰了通常睡觉。这种设计将使我们能够确定CFS，疾病而不是疾病的症状是否导致细胞因子模式改变。在受试者执行最大运动测试以及在完全睡眠剥夺的晚上，我们将重复整个协议。我们预计，已知会加剧CFS症状的运动将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患者中产生睡眠的细胞因子来放大差异，但在患者中没有睡眠不足。