环孢素免疫抑制作用的药效动力学监测

目的：以不同的T淋巴细胞功能标志物作为药效动力学指标．探讨环孢素（CsA）免疫抑制作用监测的可能性。方法：采用淋巴细胞体外培养与刺激的方法．分别在正常人外周全血中加入不同浓度（0、10、50、100和200nmol／L）的CsA．然后加入一定浓度的刀豆蛋白A刺激培养：一段时间后分离出淋巴细胞．以流式细胞术检测代表不同T淋巴细胞功能的细胞表面标记（CD25、CD28、CD54）的表达水平和T淋巴细胞内IL-2水平。分析5例健康人．各个药效动力学指标均取均值．以SPSS 13．0作相关性分析。结果：CD25与CsA剂量之间的相关系数r=-0．949．r^2=0．901．P=0．014〈0、05;CD28与CsA剂量之间的相关系数r=0．402,r^2=0．162,P=0．502〉0．05;CD54与CsA剂量之间的相关系数r=-0．974,r2=0．949,P=0．005〈0．01;IL-2与CsA剂量之间的相关系数r=-0．652．r2=0．425．P=0．233〉0．05。CD25和CD54与CsA剂量之间存在较好的负相关,具有显著性意义;而CD28、IL-2与CsA剂量之间相关性较差．不具有显著性意义。所有标志物均显示．在不同的药物浓度作用点上个体间均存在广泛的差异。结论：选择合适的T淋巴细胞功能标志物作为药效动力学指标,有可能对CsA免疫抑制作用进行监测．从而提升CsA治疗的功效和安全性。

Pharmacodynamic monitoring of the immunosuppressive effects of cyclosporine

Objective To explore the possibility of pharmacodynamic monitoring of cyclosporine immuno-suppression by measuring T-cell functions in peripheral whole blood.Methods Different concentrations of CsA(0,10,50,100,200 nmol/L) were added to peripheral whole blood from five normal human volunteers.After concanavalin-A stimulation and culture,the whole blood samples were analyzed by flow cytometry detecting T-cell surface antigen markers(CD25,CD28,CD54) and the expression of intracellular IL-2.Data analysis was performed by software SPSS 13.0.Results We found that the percent of T-cell expressing CD25 or CD54 decreased in a CsA dose-dependent manner,and the percent of T-cell expressing IL-2 or CD28 did not.The coefficients of determination(r2) between the magnitude of drug concentrations and the magnitude of induction in percent of T-cell expressing CD25,CD54,CD28 or IL-2 were 0.901,0.949,0.162 and 0.425,respectively.We also found that there were considerable differences in the responses to CsA between individuals,regardless of the CsA dosage.Conclusion The results suggest that immunosuppression of CsA may be appropriately monitored by measuring T-cell function in peripheral whole blood,and the assay could promote efficacy and safety of CsA in clinics.