Evaluation of Interleukin-2 mRNA in Whole Blood as a Parameter for Monitoring Cyclosporine Pharmacodynamics
Evaluation of Interleukin-2 mRNA in Whole Blood as a Parameter for Monitoring Cyclosporine Pharmacodynamics
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DOI：
10.1248/bpb.32.604
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发表时间：
2009-04-01
影响因子：
2
通讯作者：
Yamada, Kiyofumi
中科院分区：
文献类型：
--
作者：
Kuzuya, Takafumi;Kobayashi, Takaaki;Yamada, Kiyofumi
抑制细胞因子的产生是环孢素(CsA)的主要免疫抑制作用，广泛应用于器官移植。用于评估每位患者白介素 2 (IL-2) 产生抑制情况的药效 (PD) 测定可以提供更合适的给药方案。我们通过实时逆转录聚合酶链式反应 (RT-PCR) 方法测量了添加一定浓度的 CsA 后全血中 IL-2 mRNA 表达的抑制情况。在体外和离体健康受试者中评估个体 CsA 对 IL-2 mRNA 表达的敏感性。我们还在移植前患者服用免疫抑制药物之前对其进行了评估。采用Sigmoid E-max模型分析CsA浓度与IL-2 mRNA表达量的关系。测定在8小时内完成。导致 IC50 的浓度在健康受试者中显示出高重现性和特异性 (p
Inhibition of cytokine production is the main immunosuppressive effect of cyclosporine (CsA), which is widely used in organ transplantation. Pharmacodynamic (PD) assay for evaluating the inhibition of interleukin-2 (IL-2) production for each patient could provide a more appropriate dosing regimen. We measured the suppression of IL-2 mRNA expression in whole blood following the addition of a range of CsA concentrations by a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Individual CsA sensitivity on the IL-2 mRNA expression was assessed with healthy subjects both in vitro and ex vivo. We also evaluated it in pre-transplant patients before taking immunosuppressive drugs. Sigmoid E-max model was used to analyze the relationship between CsA concentration and IL-2 mRNA expression. The assay was completed within 8 h. The concentration that resulted in IC50 showed high reproducibility and specificity among the healthy subjects (p