Lin Ying, Zhou Xieming, Guo Wenjian, Li Qianqian, Pan Xiahui, Bao Yunhua, He Muqing, Zhu Baoling, Lin Xiaoji, Jin Limin, Yao Rongxin
Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
The 117th hospital PLA Hangzhou, China.
Int Immunopharmacol. 2016 Sep;38:40-4. doi: 10.1016/j.intimp.2016.05.002. Epub 2016 May 26.
Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation.
免疫性血小板减少症(ITP)是一种自身免疫性出血性疾病,其特征为血小板计数减少。据报道,ITP患者中存在辅助性T细胞1(Th1)细胞极化,Th1/Th2比值增加。这种转变与T细胞中表达的转录因子T盒(T-bet)上调和GATA结合蛋白3(GATA-3)下调有关,导致T-bet/GATA-3比值增加。我们之前的体外研究表明,重组人白细胞介素-11(rhIL-11)可以使从成年ITP患者分离的外周血单个核细胞(PBMC)中的Th1/Th2失衡恢复正常,同时T-bet/GATA-3比值也恢复正常。在本报告中,我们研究了rhIL-11对临床ITP患者是否具有治疗作用,以及rhIL-11治疗是否能在体内使Th1/Th2和T-bet/GATA-3水平恢复正常。我们发现,rhIL-11治疗的有效率为67.7%,在反应良好的ITP患者中,Th1和T-bet水平显著降低,但Th2和GATA-3水平升高,Th1/Th2和T-bet/GATA-3比值恢复正常,与健康对照相似。因此,我们的研究表明rhIL-11对ITP有效且不良反应可耐受。该治疗策略值得进一步进行临床研究。