CHRONIC EPSTEIN BARR VIRUS INFECTION AND CHRONIC FATIGUE SYNDROME

慢性爱泼斯坦巴尔病毒感染和慢性疲劳综合症

• 批准号: 3790763
• 负责人: S E STRAUS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790763
• 关键词: Epstein Barr virus; acyclovir; adrenocorticotropic hormone; arginine vasopressin; artificial immunosuppression; catechols; child (0-11); chronic fatigue syndrome; clinical trials; corticotropin releasing factor; cortisol; disease /disorder classification; hormone therapy; human subject; human therapy evaluation; hypothalamic pituitary axis; interferons; lymphocyte proliferation; neuroendocrine system; neuropeptides; pituitary adrenal axis

The goals of this project are to characterize severe chronic infections with Epstein Barr Virus (EBV) and to characterize multiple aspects of the chronic fatigue syndrome which was, earlier, considered to be related to EBV infection. To date this research project has involved nearly 190 patients. Included are 7 patients who were diagnosed with severe chronic EBV infections on the basis of clinical, histological molecular and serologic features. We continue to examine immunologic features of patients with severe chronic EBV-associated lymphoproliferation and explore treatments. Acyclovir, alpha and gamma interferons proved of little value, but immunosuppressive therapies are being used with good long term results. Detailed immunologic, neurologic, endocrinologic and psychologic studies are being conducted on selected patients with chronic fatigue. To date we still have no consistent laboratory abnormality that permits a clear diagnosis of the chronic fatigue syndrome, however, we have been pursuing the basis and meaning of the group abnormalities in neuropsychiatric, immune and endocrine systems. A series of studies of the pituitary- adrenal responsiveness to corticotropin releasing hormone and ACTH and of neuropeptide and catechol levels in spinal fluid suggest a novel neuroendocrine defect that may indicate deficient central CRH release. Since CRH induces CNS arousal, these neuroendocrine findings suggest a new mechanism whereby the lethargy of Chronic Fatigue Syndrome patients may be explained. We are pursuing these observations in a new series of studies and a fresh patient cohort. Arginine-Vasopressin infusions are being given to stimulate and test the HPA axis. A placebo-controlled trial of hydrocortisone treatment has begun. It should permit us to test the hypothesis that corticosteroid deficit leads to symptoms. We also recognized discrete abnormalities in CFS patient lymphocyte phenotype and in vitro responsiveness to mitogens in patterns suggesting mild immune activation. There is a reduction in naive (CD4xCD45RA) T cells and an increase in memory (CD4xCD45RO) T cells bearing adhesion markers (LFA3, CD29, etc.).

该项目的目标是描述严重慢性感染的特征 与Epstein巴尔病毒（EBV）的感染，并表征 慢性疲劳综合征，早期被认为与 EB病毒感染。 迄今为止，该研究项目已涉及近190个 患者 包括7例被诊断为严重慢性 根据临床、组织学、分子生物学和 血清学特征 我们将继续研究 患有严重慢性EBV相关淋巴细胞增生的患者， 探索治疗方法。 阿昔洛韦，α和γ干扰素证明， 几乎没有价值，但免疫抑制疗法正在使用， 长期结果。 详细的免疫学、神经学、内分泌学和心理学研究 正在对选定的慢性疲劳患者进行研究。 目前为止我们 仍然没有一致的实验室异常， 慢性疲劳综合征的诊断，然而，我们一直在追求 神经精神科群体性异常的基础和意义， 免疫和内分泌系统。 一系列关于脑垂体的研究- 肾上腺对促肾上腺皮质激素释放激素和ACTH的反应性， 脊髓液中的神经肽和儿茶酚水平表明， 神经内分泌缺陷可能表明中枢CRH释放不足。 由于CRH诱导中枢神经系统觉醒，这些神经内分泌研究结果表明， 慢性疲劳综合征患者的嗜睡可能是一种机制， 解释道 我们在一系列新的研究中继续这些观察 和一个新的病人群体 精氨酸加压素注射液 刺激和测试HPA轴。 在安慰剂对照试验 氢化可的松治疗已经开始 它应该可以让我们测试 皮质类固醇缺乏导致症状的假设。 我们也 在CFS患者淋巴细胞表型中识别出离散异常， 体外对有丝分裂原的反应性表明， activation. 幼稚（CD 4xCD 45 RA）T细胞减少， 携带粘附标志物（LFA 3， CD 29等）。