Immune Modulation of Autoimmunity by Herbal Products

描述(由申请人提供)：根据5年前的调查，至少36%的美国成年人每年都会采用某种形式的补充和替代医学(CAM)疗法来满足他们的医疗需求(2002年全国访谈健康调查，CDC)。在CAM模式中，使用自然生长的植物产品作为有效的治疗实体，以及与传统使用的药物相比，草药的毒性相对较低，在西方世界普及了植物配方的消费。尽管草药被广泛使用，但大多数草药的作用机制仍不清楚。我们利用自身免疫的实验模型进行的初步研究表明，中草药南蛇藤可抑制临床疾病，并诱导抗原特异性免疫反应的显著变化(例如，细胞因子反应从促炎型转变为抗炎型，并增加抗原性抗体的产生)。在这项研究中，我们提出了一些实验，以测试南蛇舌草通过CD4CD25T调节细胞(Treg)、体内淋巴细胞向靶器官的运输、保护性抗体和炎症介质诱导免疫调节的深入机制。在这方面，我们的建议非常符合RFA-AT-08-003的目标。目的1.研究补体对小鼠外周血中CD_4~(2+)、CD_(25)~(25)T细胞的抑制作用，探讨其对疾病进程的下调作用。目的2.研究南蛇藤减少潜在致病T细胞向靶器官迁移的机制。目的3.确定对疾病相关抗原增强的抗体反应如何导致自身免疫反应的抑制。目的4.检测苦参素对靶组织炎症介质的调节作用。虽然这一建议涉及一种CAM模式(一种中药)和一种自身免疫的实验模型，但我们相信我们研究中阐明的基本机制原理也将部分适用于其他CAM模式以及其他自身免疫模式。 公共卫生相关性：天然植物产品越来越多地被患有各种自身免疫性疾病的患者使用，如糖尿病、多发性硬化症、关节炎和狼疮。然而，这些产品中的许多作用机制还没有定义。我们建议研究中草药南蛇藤对自身免疫的有利作用的免疫系统相关机制。我们将在自身免疫的实验模型中进行这些研究。我们的研究结果将有助于利用植物产品开发合理设计的自身免疫治疗方法。

DESCRIPTION (provided by applicant): At least 36 percent of adult Americans adopted some form of complementary and alternative medicine (CAM) therapy for their healthcare needs annually as surveyed 5 years ago (National Interview Health Survey of 2002, CDC). Among CAM modalities, the use of naturally grown plant products as efficacious therapeutic entities as well as the relative lack of toxicity of herbs compared to conventionally used drugs has popularized the consumption of botanical formulas in the western world. Despite the extensive use of medicinal herbs, the mechanisms of action remain unclear for most of them. Our preliminary study using an experimental model of autoimmunity has revealed that the Chinese herb Celastrus suppresses clinical disease and induces significant changes in antigen-specific immune response (e.g., deviation of the cytokine response from pro-inflammatory to anti-inflammatory type, and increased production of antigenspecific antibodies). In this study, we have proposed experiments to test the in-depth mechanisms of Celastrus-induced immune modulation operative via the CD4+CD25+ T regulatory cells (Treg), the in vivo trafficking of lymphocytes into the target organ, the protective antibodies, and the inflammatory mediators. In this respect, our proposal is an excellent match with the objectives of RFA-AT-08-003. Aim 1. To study the suppressive function of CD4+CD25+T cells that leads to the downregulation of the disease process in Celastrus-fed rats. Aim 2. To examine the mechanisms by which Celastrus reduces the migration of potentially pathogenic T cells into the target organ. Aim 3. To determine how enhanced antibody response to the disease-related antigen leads to suppression of the autoimmune response. Aim 4. To test for the Celastrus-induced modulation of inflammatory mediators in the target tissue. Although this proposal involves one CAM modality (a Chinese herb) and one experimental model of autoimmunity, we believe that the basic mechanistic principles elucidated in our study would also be applicable in part to other CAM modalities as well as other models of autoimmunity. Public Health Relevance: Natural plant products are increasingly being used by patients with a variety of autoimmune diseases, such as diabetes, multiple sclerosis, arthritis and lupus. However, the mechanisms of action of many of these products are not defined. We propose to study the immune system related mechanisms by which Celastrus, a Chinese herb, mediates its beneficial effects against autoimmunity. We will conduct these studies in an experimental model of autoimmunity. The results of our study would help developing rationally designed therapeutic approaches for autoimmunity using botanical products.