Zhang Xiaohui, Zhou Yi, Xu Lanping, Han Wei, Chen Huan, Chen Yuhong, Fu Haixia, Zhou Shiyuan, Zhao Jingzhong, Wang Qianming, Feng Feier, Zhu Xiaolu, Liu Kaiyan, Huang Xiaojun
Institute of Hematology, Peking University People's Hospital, Peking University, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China,
Ann Hematol. 2015 May;94(5):837-45. doi: 10.1007/s00277-014-2278-7. Epub 2014 Dec 16.
Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III-IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I-II aGVHD (40.26 ng/ml, p < 0.01) or patients without aGVHD (41.40 ng/ml, p < 0.05). Allografts, including granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cell (PBPC) and G-CSF-primed bone marrow (GBM), from 38 patients were analyzed for IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.
急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）相关的主要并发症。白细胞介素（IL）-35是一种可抑制免疫反应的新型抗炎细胞因子。这项前瞻性研究探讨了65例HSCT术后患者的IL-35血浆水平。结果显示，与I-II级aGVHD移植患者（40.26 ng/ml，p<0.01）或无aGVHD患者（41.40 ng/ml，p<0.05）相比，III-IV级aGVHD患者外周血中的IL-35水平降低（23.46 ng/ml）。对38例患者的同种异体移植物进行了分析，包括粒细胞集落刺激因子（G-CSF）动员的外周血祖细胞（PBPC）和G-CSF预处理的骨髓（GBM），以检测与aGVHD相关的IL-35水平。在GBM中接受较低水平IL-35细胞（28.0 ng/ml，p=0.551）或在PBPC中接受较低水平IL-35（53.46 ng/ml，p=0.03）的患者aGVHD发病率更高。aGVHD患者的血小板聚集增加。在体外将IL-35添加到患者血液中，IL-35以剂量依赖的方式抑制血小板聚集。血小板活化标志物（CD62P/PAC-1）也可被IL-35抑制。结果表明，IL-35可能通过抑制血小板活化和聚集来影响aGVHD的发展。我们的数据表明，IL-35是allo-HSCT术后对抗aGVHD的一种潜在有效治疗药物。
