CENTER FOR MULTIDISCIPLINARY STUDIES OF CFS PATHOGENESIS

最近，我们对CFS中神经内分泌介质的了解取得了进展，但提出的问题多于答案。当然，有两个研究领域突出且相互交织：直立性低血压生物学和反应性生物学。在该中心的申请中提出了几点新的看法，这四个项目将相辅相成，就像拼图的碎片一样，使对中心的整体情况和理解更加清晰。项目I研究了导致低红细胞质量的自主神经机制，以及CFS相关细胞因子抑制促红细胞生成素产生的可能性。这导致了一项关于红细胞质量扩张、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使用血液容量操作来研究CFS中自主神经和心血管相互作用的机制，并与项目I共享数据以获得共享研究人群的完整图景。项目2还通过认知行为应激管理范式改变应激反应，并评估其对疾病的潜在媒介，如免疫功能和炎性细胞因子产生的影响，从而操纵CFS的生物学。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)和炎性细胞因子(TNF-(X)在分子水平上对NK细胞功能的作用。这些项目每个都将得到行政、卫生、心理社会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.