Impact of single immunosuppressive drug withdrawal on lymphocyte immunoreactivity.
Impact of single immunosuppressive drug withdrawal on lymphocyte immunoreactivity.
复制标题
单一免疫抑制药物停药对淋巴细胞免疫反应性的影响。
DOI：
10.1016/j.jss.2013.11.1085
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Perkins,David
中科院分区：
文献类型：
--
作者：
Verma,Meenakshi;Awdishu,Linda;Lane,James;Park,Ken;Bahur,Bayda;Lwin,Wint;McGee,Halvor;Steiner,Robert;Finn,Patricia;Perkins,David
背景慢性排斥反应是肾移植受者移植物失功的主要原因.不依从药物治疗是公认的慢性排斥反应的原因，导致长期移植物功能障碍和移植受体失败。需要频繁给药的半衰期短的免疫抑制药物，如他克莫司，使移植方案复杂化，并可能增加不依从性。使用半衰期长的药物，如西罗莫司，每日给药一次，可以简化治疗方案。单药缺失剂量的影响尚未得到广泛研究。不稳定的遵守或暂时停止免疫抑制药物可能有显着的影响慢性reject.MethodsOur研究评估的影响，单药撤回常用的免疫抑制剂（西罗莫司和他克莫司）对淋巴细胞的反应。我们分析了淋巴细胞增殖，细胞因子分泌，和腺苷三磷酸生成使用交叉研究设计与正常健康患者。淋巴细胞增殖进行了评估，使用5-溴-2-脱氧尿苷掺入，和T细胞功能进行了分析，通过检查腺苷三磷酸generation. ResultsWe的结果表明，西罗莫司发挥长期抑制淋巴细胞增殖和减少白细胞介素17 A，持续到48小时后停药。相比之下，他克莫司并没有类似的淋巴细胞增殖或白细胞介素17 A的secrety.ConclusionFuture西罗莫司在不同移植人群的分析值得调查。
BackgroundChronic rejection is a major cause of graft loss in kidney transplant recipients. Nonadherence to drug therapy is a well-recognized cause of chronic rejection leading to long-term graft dysfunction and failure for transplant recipients. Immunosuppressive medications with short half-lives that require frequent dosing, such as tacrolimus, complicate transplant regimens and may increase noncompliance. Regimens could be simplified using drugs with long half-lives requiring once-daily administration, such as sirolimus. The impact of missing doses of single agents has not been studied extensively. Erratic compliance or temporary discontinuation of immunosuppressive drugs may have significant implications for chronic rejection.MethodsOur study evaluated the impact of single drug withdrawal of commonly used immunosuppressive agents (sirolimus and tacrolimus) on lymphocyte responses. We analyzed lymphocyte proliferation, cytokine secretion, and adenosine triphosphate generation using a crossover study design with normal healthy patients. Lymphocyte proliferation was assessed using 5-bromo-2-deoxyuridine incorporation, and T cell function was analyzed by examining adenosine triphosphate generation.ResultsOur results indicate that sirolimus exerts prolonged suppression of lymphocyte proliferation and decreased interleukin 17A that lasts up to 48 h after drug withdrawal. In comparison, tacrolimus did not have a similar effect on lymphocyte proliferation or interleukin 17A secretion.ConclusionFuture analysis of sirolimus in diverse transplantation populations merits investigation.