Qu Ming-Ming, Liu Xue-Na, Liu Xin-Guang, Feng Qi, Liu Yang, Zhang Xu, Liu Shuang, Zhang Lei, Li Guo-Sheng, Zhu Yuan-Yuan, Lv Ming-Yun, Peng Jun, Hou Ming
Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, PR China.
Cytokine. 2017 Apr;92:110-117. doi: 10.1016/j.cyto.2017.01.013. Epub 2017 Jan 29.
Thrombopoietin receptor agonists (TPO-RAs) have been clinically used in primary immune thrombocytopenia (ITP) with favorable outcomes, while their effect on cytokine regulation in ITP remains unknown. In the present study, plasma and mRNA expression levels of interleukin (IL)-2, interferon gamma (IFN-γ), IL-4, IL-17A, and transforming growth factor-β1 (TGF-β1) were determined by ELISA and real-time quantitative PCR in 26 corticosteroid-resistant/relapsed ITP patients receiving eltrombopag or rhTPO therapy and 15 healthy controls (HCs). Results showed that plasma and mRNA levels of IL-2, IFN-γ, IL-4, and IL-17A in ITP patients did not change significantly after TPO-RA treatment, whereas TGF-β1 levels increased remarkably. The pre- and post-treatment plasma and mRNA levels of IFN-γ and IL-2 were significantly higher, while the pre- and post-treatment IL-4 levels as well as the pre-treatment TGF-β1 levels were remarkably lower in ITP patients compared with HCs. There was no significant difference in TGF-β1 levels between TPO-RA-treated ITP patients and HCs. No statistical difference was found in plasma levels of IL-17A between ITP patients before or after treatment and HCs. However, the pre- and post-treatment mRNA expression of IL-17A and retinoic orphan receptor (ROR) γt in ITP patients were higher than that in HCs. Overall, these findings indicated that TPO-RA treatment could promote the secretion of TGF-β1, while it could not correct the Th1 and Th17 polarization in ITP patients. This study might improve our understanding of the mechanism of action of TPO-RAs and provide important information for optimizing therapeutic strategies for ITP.
血小板生成素受体激动剂（TPO-RAs）已在原发性免疫性血小板减少症（ITP）中临床应用并取得了良好疗效，但其对ITP中细胞因子调节的影响仍不清楚。在本研究中，通过酶联免疫吸附测定（ELISA）和实时定量聚合酶链反应（PCR），测定了26例接受艾曲泊帕或重组人血小板生成素（rhTPO）治疗的糖皮质激素抵抗/复发ITP患者及15名健康对照者（HCs）血浆和mRNA中白细胞介素（IL）-2、干扰素γ（IFN-γ）、IL-4、IL-17A和转化生长因子-β1（TGF-β1）的表达水平。结果显示，TPO-RA治疗后ITP患者血浆和mRNA中IL-2、IFN-γ、IL-4和IL-17A水平无明显变化，而TGF-β1水平显著升高。与HCs相比，ITP患者治疗前后血浆和mRNA中IFN-γ和IL-2水平显著更高，而治疗前后IL-4水平以及治疗前TGF-β1水平显著更低。接受TPO-RA治疗的ITP患者与HCs之间TGF-β1水平无显著差异。ITP患者治疗前后与HCs之间IL-17A血浆水平无统计学差异。然而，ITP患者治疗前后IL-17A和视黄酸孤儿受体（ROR）γt的mRNA表达高于HCs。总体而言，这些发现表明TPO-RA治疗可促进TGF-β1分泌，但不能纠正ITP患者的Th1和Th17极化。本研究可能会增进我们对TPO-RAs作用机制的理解，并为优化ITP治疗策略提供重要信息。
