Chen Danyan, Huang Xiaolong, Lu Song, Gan Hua, Tang Weixue, Liu Ke
Department of Endocrinology and Nephrology, The Chongqing Zhongshan Hospital, Chongqing 400013;
Department of Neurosurgery, No. 324 Hospital of PLA, Chongqing 400028;
Biomed Rep. 2013 May;1(3):413-419. doi: 10.3892/br.2013.63. Epub 2013 Jan 31.
Investigations of Treg/Th17 imbalance associated with cardiovascular complications in hemodialysis are limited. The aim of this study was to examine the association between Treg/Th17 balance and cardiovascular comorbidity in maintenance hemodialysis (MHD). Uremic patients included in the present study were divided into three groups: the WHD group comprising 30 patients with no cardiovascular complications or maintenance hemodialysis (MHD), the MHD1 group comprising 36 patients presenting with cardiovascular complications during MHD, and the MHD2 group comprising 30 patients with a lack of cardiovascular complications during MHD. The control group comprised 20 healthy volunteers. Th17 and Treg cells were measured by fluorescence-activated cell scanning (FACS). IL-6 and IL-10 levels were determined by enzyme-linked immunosorbent assay (ELISA). Monocyte surface expression of the costimulatory molecules CD80 and CD86 was assessed by FACS after the monocytes were cocultured with Th17 or Treg cells in the presence or absence of IL-17. Results revealed that the percentage of Th17 of total CD4(+) cells was significantly higher in the MHD1 (36.27±9.62% in) and WHD (35.98±8.85%) groups compared with the MHD2 (19.64±5.97%) and healthy (1.12±1.52%) groups. Elevated IL-6 levels were obtained in Th17 cells for the MHD1 and WHD groups, whereas a marked decrease was evident when IL-17 was blocked. However, no significant differences or cardiovascular complications were detected in the expression of CD80 and CD86 in the MHD group, whereas the expression of the uremic subgroups was statistically higher compared with the healthy controls. To the best of our knowledge, this is the first study to demonstrate that the Treg/Th17 imbalance may be associated with the pathogenesis of cardiovascular complications in uremic patients undergoing hemodialysis through the B7-independent upregulation of IL-6 induced by IL-17.
关于血液透析中与心血管并发症相关的调节性T细胞(Treg)/辅助性T细胞17(Th17)失衡的研究有限。本研究旨在探讨维持性血液透析(MHD)中Treg/Th17平衡与心血管合并症之间的关联。纳入本研究的尿毒症患者分为三组:WHD组,包括30例无心血管并发症或维持性血液透析(MHD)的患者;MHD1组,包括36例在MHD期间出现心血管并发症的患者;MHD2组,包括30例在MHD期间无心血管并发症的患者。对照组包括20名健康志愿者。通过荧光激活细胞扫描(FACS)检测Th17和Treg细胞。采用酶联免疫吸附测定(ELISA)法测定白细胞介素-6(IL-6)和白细胞介素-10(IL-10)水平。在有或无IL-17存在的情况下,将单核细胞与Th17或Treg细胞共培养后,通过FACS评估共刺激分子CD80和CD86在单核细胞表面的表达。结果显示,与MHD2组(19.64±5.97%)和健康组(1.12±1.52%)相比,MHD1组(36.27±9.62%)和WHD组(35.98±8.85%)中CD4(+)细胞总数中Th17的百分比显著更高。MHD1组和WHD组的Th17细胞中IL-6水平升高,而当IL-17被阻断时,IL-6水平明显下降。然而,MHD组中CD80和CD86的表达未检测到显著差异或心血管并发症,而尿毒症亚组的表达与健康对照组相比在统计学上更高。据我们所知,这是第一项证明Treg/Th17失衡可能通过IL-17诱导的不依赖B7的IL-6上调与接受血液透析的尿毒症患者心血管并发症的发病机制相关的研究。