SLEEP AND CYTOKINES IN RHEUMATOID ARTHRITIS: AN EXAMINATION OF THE EFFECTS OF

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标： 1.比较类风湿关节炎患者与健康对照组睡眠宏观结构和微观结构的差异。以前的研究已经发现了类风湿性关节炎患者睡眠障碍的证据，这与晚上疼痛的作用无关(Drewes等人。1998年)。我们将扩展先前依赖于传统视觉阶段评分的研究，使用计算机分析睡眠EEG，并提供对类风湿关节炎患者和对照组睡眠期间大脑活动的更完整描述。 2.确定睡眠和早晨促炎细胞因子表达水平与早晨僵硬、疲劳和疼痛的日间症状之间的关系。在醒来后，将检测类风湿性关节炎和健康对照组的循环IL-6和肿瘤坏死因子的水平和刺激表达。此外，对于类风湿性关节炎受试者，将评估睡眠与关节僵硬、疼痛和整体疲劳等症状之间的关系。 3.建立促炎细胞因子对类风湿关节炎患者睡眠障碍的预测效度。我们将评估在类风湿性关节炎和健康对照组中，促炎症细胞因子在睡眠开始前的表达是否可以预测睡眠的数量和深度，而与晚上的疼痛无关。此外，随后将对类风湿性关节炎受试者进行睡眠评估，其中将使用一种肿瘤坏死因子拮抗剂，以实验性地探索夜间促炎细胞因子对睡眠质量和深度的作用。肿瘤坏死因子拮抗剂降低了生物可利用的肿瘤坏死因子和血清IL-6水平(Feldmann和Maini，1999)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: 1. To compare differences in sleep macro- and microarchitecture in rheumatoid arthritis patients and healthy controls. Previous investigations have found evidence of disordered sleep in rheumatoid arthritis, independent of the contribution of evening pain (Drewes et al. 1998). We will extend prior studies that have relied on traditional visual stage scoring, use computer analysis of sleep EEG, and provide a more complete description of brain activity during sleep in rheumatoid arthritis patients and controls. 2. To determine the association between sleep and morning levels of pro-inflammatory cytokine expression and daytime symptoms of morning stiffness, fatigue and pain. Upon waking, circulating levels and stimulated expression of IL-6 and TNF will be examined in both rheumatoid arthritis and healthy control subjects. Furthermore, for rheumatoid arthritis subjects, relationships between sleep and symptoms such as joint stiffness and pain and overall fatigue will be assessed. 3. To establish the predictive validity of pro-inflammatory cytokines for disordered sleep in rheumatoid arthritis. We will evaluate whether the expression of pro-inflammatory cytokines prior to sleep onset predicts sleep amount and depth, independent of evening pain, in both rheumatoid arthritis and healthy control groups. In addition, subsequent sleep assessments with the rheumatoid arthritis subjects will be conducted in which a TNF antagonist will be administered to experimentally probe the action of nocturnal pro-inflammatory cytokines on sleep quality and depth. TNF antagonism decreases biologically available TNF and serum levels of IL-6 (Feldmann and Maini 1999).