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，但尚未在移植背景下进行研究。我们计划利用古老的东方草药知识，了解所选植物在移植中的作用机制以及免疫抑制药物和植物之间的相互作用。我们研究了几种常用的草药产品，发现一些抑制和其他刺激体外淋巴细胞增殖。我们专注于两种产品;生姜抑制和奶蓟刺激有丝分裂原和所有抗原挑战的淋巴细胞增殖。在人和鼠淋巴细胞中一致观察到这些效应。姜和奶蓟的抑制和刺激机制似乎分别增加了Th 2和Th 1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，天然存在的草药产品可以调节免疫系统，这些产品将是临床上有用的，因为它们的整体行动和低毒性。更具体地说，我们假设生姜将抑制和奶蓟将刺激对所有抗原的体内免疫反应，包括心脏移植物中的抗原。我们将通过在小鼠心脏移植的临床相关模型中使用这些草药的标准化制剂来检验这一假设。我们希望生姜能延长同种异体移植物的存活时间，而奶蓟会缩短这些移植物的存活时间。我们还建议在心脏移植模型中测试这两种草药与常规免疫抑制剂如环孢素A的相互作用。 我们的实验将全面地确定草药产品是否能调节移植免疫力。他们还将揭示生姜和奶蓟的作用机制，确定这些草药产品是否与传统的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.