NEUROENDOCRINE REGULATION AND EFFECTS ON IMMUNE FUNCTION

神经内分泌调节及其对免疫功能的影响

• 批准号: 3083760
• 负责人: ANTHONY T REDER
• 金额: $ 6.45万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-06 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3083760
• 关键词: adrenocorticotropic hormone; dexamethasone; glucocorticoids; histocompatibility antigens; hormone receptor; human tissue; immunofluorescence technique; immunoregulation; lymphocyte; multiple sclerosis; neuroendocrine system; psychoneuroimmunology; surface antigens; tissue /cell culture

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with involvement of the immune system. Steroids and ACTH have been used to treat MS but are effective only in a subgroup of patients. I have found that 50% of MS patients have abnormal regulation of serum cortisol levels as defined by the dexamethasone suppression test (DST). These nonsuppressors may compose the subgroup of patients who fail to respond to ACTH therapy. In earlier work with depressed patients, we demonstrated that cortisol nonsuppression is coincident with lymphocyte insensitivity to steroids in vitro and failure of lymphocyte glucocorticoid (GCC) receptor down regulation in vivo. This is relevant to MS in that MS patients have an increased incidence of depression and also have abnormalities in cortisol autoregulation. I propose to further investigate the relationship between abnormal cortisol responses in vivo (DST) and therapeutic and immunologic variables including the following: clinical response to ACTH therapy; lymphocyte surface antigens, immune function, and responses to steroids in vitro; and GCC receptor resonses to steroids in vivo and in vitro. In addition, we will study the ability of MS lymphocytes to secrete ACTH in tissue culture and in response to in vivo stimuli (i.e. exacerbation of MS). This lymphocyte production of ACTH will be related to the level of serum cortisol in MS patients and to direct effects of ACTH on lymphocytes to determine its biological significance. Through these assays, we hope to predict clinical responses to steroid therapy and to define basic neuroendocrine and immunological factors involved in the pathogenesis of MS. These studies should enhance understanding of a spectrum of neuroendocrine effects on immune function and immune-mediated disease.

多发性硬化症（MS）是一种中枢神经脱髓鞘疾病 免疫系统参与的系统。 类固醇和 ACTH 已 用于治疗多发性硬化症，但仅对一小部分患者有效。 我发现50%的多发性硬化症患者血清调节异常 皮质醇水平由地塞米松抑制试验 (DST) 定义。 这些非抑制者可能构成未能抑制的患者亚组。 对 ACTH 治疗有反应。 在早期针对抑郁症患者的工作中，我们 证明皮质醇非抑制与淋巴细胞一致 体外对类固醇不敏感和淋巴细胞糖皮质激素失效 (GCC) 受体体内下调。 这与 MS 相关 患者抑郁症的发病率增加，并且 皮质醇自动调节异常。 我建议进一步研究异常皮质醇之间的关系 体内反应（DST）以及治疗和免疫学变量，包括 以下：对 ACTH 治疗的临床反应；淋巴细胞表面 抗原、免疫功能和体外类固醇反应；和海湾合作委员会 受体在体内和体外对类固醇产生反应。 此外，我们将 研究组织培养中 MS 淋巴细胞分泌 ACTH 的能力 对体内刺激的反应（即 MS 恶化）。 这个淋巴细胞 MS 中 ACTH 的产生与血清皮质醇水平有关 患者并直接影响 ACTH 对淋巴细胞的影响以确定其 生物学意义。 通过这些测定，我们希望预测临床 对类固醇治疗的反应并定义基本的神经内分泌和 免疫学因素参与 MS 的发病机制。 这些研究 应加强对一系列神经内分泌影响的理解 免疫功能和免疫介导的疾病。