Relevance of Herbal Products in Transplantation

描述(由申请人提供)：草药产品在美国的使用越来越多：1500万人面临与草药产品发生药物相互作用的风险。其中一些产品会影响免疫系统，但尚未在移植的背景下进行研究。我们计划利用古老的东方草药知识，了解选定的植物药物在移植中的作用机制，以及免疫抑制药物和植物药物之间的相互作用。我们研究了几种常用的中草药产品，发现一些抑制淋巴细胞增殖，另一些则在体外促进淋巴细胞增殖。我们重点研究了两种产品：抑制细胞增殖的生姜和刺激淋巴细胞增殖的水飞蓟，这些细胞受到有丝分裂原和所有抗原的挑战。这些效应在人类和小鼠的淋巴细胞中一直都能观察到。其抑制和刺激机制可能分别是生姜和水飞蓟增加Th2和Th1细胞因子的分泌。我们已经开始研究生姜在小鼠心脏移植模型中的作用。 我们的假设是，天然草药产品可以调节免疫系统，这些产品将因其整体作用和低毒性而在临床上有用。更具体地说，我们假设生姜会抑制，而水飞蓟会刺激体内对所有抗原的免疫反应，包括心脏移植物中的抗原。我们将在临床相关的小鼠心脏移植模型中使用这些草药的标准化制剂来验证这一假设。我们预计生姜可以延长移植物的存活时间，而水飞蓟则会缩短移植物的存活时间。我们还建议在心脏移植模型中测试这两种中药与传统免疫抑制药物如环孢素A的相互作用。 我们的实验将从整体上确定草药产品是否能调节移植免疫。他们还将揭示生姜和水飞蓟的作用机制，确定这些草药产品是否与传统免疫抑制药物相互作用，并可能发现新的免疫调节剂。

DESCRIPTION (provided by applicant): Herbal products are being increasingly used in the United States: 15 million people are at risk for drug interactions with the herbal products. Some of these products affect the immune system but have not been studied in the context of transplantation. We plan to understand the mechanisms of action of selected botanicals in transplantation and the interactions between immunosuppressive drugs and botanicals, taking advantage of the old Eastern herbal knowledge. We have studied several commonly used herbal products and found that some suppress and others stimulate lymphocyte proliferation in vitro. We have focused on two products; ginger which suppresses and milk thistle which stimulates the proliferation of lymphocytes challenged with mitogens and all antigens. These effects are consistently observed in human and murine lymphocytes. The mechanism of suppression and stimulation appears to be increased secretion of Th2 and Th1 cytokines by Ginger and Milk thistle respectively. We have started to study the effect of Ginger in a mouse model of cardiac transplantation. Our hypothesis is that naturally occurring herbal products can modulate the immune system and that these products will be clinically useful because of their holistic actions and low toxicities. More specifically, we hypothesize that ginger will suppress and milk thistle will stimulate the immune reaction in vivo against all antigens including those in cardiac allografts. We will test this hypothesis by using standardized preparations of these herbs in a clinically relevant model of cardiac transplantation in mice. We expect that ginger will prolong survival of the allografts while milk thistle will shorten the survival of these grafts. We also propose to the test the interaction of these two herbs with conventional immunosuppressive drugs like cyclosporine A in the model of cardiac allografts. Our experiments will determine, holistically, if herbal products modulate transplant immunity. They will also uncover the mechanisms of action of Ginger and Milk thistle, determine if these herbal products interact with conventional immunosuppressive drugs, and potentially discover novel immunomodulatory agents.