Sromova Lucie, Busek Petr, Posova Helena, Potockova Jana, Skrha Pavel, Andel Michal, Sedo Aleksi
Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U nemocnice 5, 12853 Prague 2, Czech Republic.
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University in Prague, Studnickova 7, 12000 Prague 2, Czech Republic.
Diabetes Res Clin Pract. 2016 Aug;118:183-92. doi: 10.1016/j.diabres.2016.06.020. Epub 2016 Jun 18.
To assess intraindividually the effects of DPP-IV inhibition on the subpopulations of immune cells in type 2 diabetes mellitus (DM2) patients during the course of treatment with sitagliptin.
In this open label non-randomized observational study with a control group DM2 patients were examined before the initiation of the DPP-IV inhibitor administration (sitagliptin 100mg once daily) and then after 4weeks and 12months. Inhibition of the blood plasma DPP-IV enzymatic activity was determined by a chromogenic assay, the immunophenotyping of the blood cell subpopulations was performed using flow cytometry and blood plasma cytokine concentrations were quantified using an array-based multiplex ELISA. All parameters were evaluated in relation to the entry values in individual patients.
The blood plasma DPP-IV enzymatic activity was effectively inhibited during the sitagliptin treatment. A significant decrease of the proportion of Treg cells (to 86±31% (median±SD) of entry values, p=0.001) and an increase of Th1 cells (to 120±103% (median±SD) of entry values, p=0.004) were observed after 4weeks but not after one year of the sitagliptin treatment. No changes were observed in the ratio of CD4(+)/CD8(+) cells, in the quantity of NK and Th2 cells and blood plasma cytokine levels.
Sitagliptin treatment may cause temporary changes of the proportion of lymphocyte subpopulations in patients with DM2. The consequent deregulation of the immune system should be considered as a possible cause of the eventual side effects of long term DPP-IV inhibition.
在西他列汀治疗过程中，对2型糖尿病（DM2）患者体内二肽基肽酶-IV（DPP-IV）抑制作用对免疫细胞亚群的个体内效应进行评估。
在这项设有对照组的开放标签非随机观察性研究中，DM2患者在开始给予DPP-IV抑制剂（西他列汀100mg，每日一次）之前接受检查，然后在4周和12个月后再次接受检查。通过显色测定法测定血浆DPP-IV酶活性，使用流式细胞术对血细胞亚群进行免疫表型分析，并使用基于阵列的多重酶联免疫吸附测定法对血浆细胞因子浓度进行定量。所有参数均相对于个体患者的初始值进行评估。
在西他列汀治疗期间，血浆DPP-IV酶活性得到有效抑制。在治疗4周后观察到调节性T细胞比例显著降低（降至初始值的86±31%（中位数±标准差），p=0.001），辅助性T细胞1（Th1）比例升高（升至初始值的120±103%（中位数±标准差），p=0.004），但在西他列汀治疗一年后未观察到上述变化。CD4(+)/CD8(+)细胞比例、自然杀伤细胞（NK）和辅助性T细胞2（Th2）数量以及血浆细胞因子水平均未发生变化。
西他列汀治疗可能导致DM2患者淋巴细胞亚群比例出现暂时变化。免疫系统的这种随之而来的失调应被视为长期DPP-IV抑制最终产生副作用的可能原因。
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