CENTER FOR MULTIDISCIPLENERY STUDIES OF CFS PATHOGENESIS

最近我们对CFS中神经内分泌介质的理解的进展提出了更多的问题而不是答案。当然，有两个领域的研究是相互交织在一起的：直立性低血压的生物学和反应性的生物学。在本中心的申请中进行了一些新颖的观察，这四个项目将以一种互补的方式相互补充，就像拼图一样，使CFS的整体图景和理解更加清晰。项目一研究自主机制，可能导致红细胞质量低，以及CFS相关细胞因子抑制促红细胞生成素产生的潜力。这导致我们对红细胞体积扩张、体积扩张和安慰剂的研究，以进一步描述我们对肾脏血流动力学的理解。项目3使用血容量操纵来研究CFS中自主神经和心血管相互作用的机制，并与项目1汇集数据，以全面了解这一共享研究人群。项目2还通过认知行为应激管理范式，通过改变应激反应来操纵CFS的生物学，并评估其对疾病潜在介质（如免疫功能和炎症细胞因子产生）的影响。项目4利用干预前干预后样本的可用性来研究CFS中自然杀伤细胞功能障碍的机制，包括应激激素（儿茶酚胺，皮质醇）和炎症细胞因子（TNF-(x)）在分子水平上对NK细胞功能的作用。这些项目将分别得到行政、卫生、社会心理和实验室评估核心单位的支持。

Recent advances in our understanding of neuroendocrine mediators in CFS have raised more questions than answers. Certainly two areas of research stand out and are intertwined: the biology of orthostatic hypotension and the biology of reactivity. Several novel observations are made in this Center application and the four projects will complement each other in a way that, like pieces of a puzzle, bring the overall picture and understanding of CFS into clearer focus. Project I examines autonomic mechanisms that would lead to the low RBC mass as well as the potential for CFS associated cytokines to inhibition erythropoietin production. This leads to a study of RBC mass expansion vs. volume expansion vs. placebo to further delineate our understanding of renal hemodynamics. Project 3 uses the blood volume manipulation to study mechanisms of autonomic and cardiovascular interactions in CFS, and pools data with Project I for a complete picture of this shared study population. Project 2 also manipulates the biology of CFS by modifying the stress response through a cognitive behavioral stress management paradigm, and evaluating its impact on potential mediators of the illness, such as immune function and inflammatory cytokine production. Project 4 capitalizes on the availability of pre intervention post intervention samples to look at mechanisms of natural killer cell dysfunction in CFS, including the role of stress hormones (catecholamines, cortisol) and inflammatory cytokines (TNF-(x) on NK cell function at the molecular level. These projects will each be supported by administrative, health, psychosocial, and laboratory assessment core units.