Li Songsong, Wu Zhenzhou, Li Ling, Liu Xuehua
Department of Rheumatism, Tianjin People's Hospital of Nankai University, Tianjin, China (mainland).
College of Life Sciences, Nankai University, Tianjin, China (mainland).
Med Sci Monit. 2016 Jun 20;22:2113-8. doi: 10.12659/msm.896355.
BACKGROUND The aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism. MATERIAL AND METHODS Thirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation. Flow cytometry was used to detect the ratio of CD4 naïve T cells and CD4 memory T cells, Th17 cells, and Treg cells in PBMC. DAS28 score, CRP, RF, and CCP levels in patients were evaluated. RESULTS Compared with before treatment, IL-6 receptor antagonist TCZ significantly improved patients' condition, including DAS28 score, CRP, RF, and CCP levels (P<0.01). Furthermore, TCZ obviously upregulated CD4 naïve T cells proportion and decreased CD4 memory T cells ratio (P<0.01). TCZ also markedly reduced the proportion of Th17 cells and increased the proportion of Treg cells (P<0.01). CONCLUSIONS TCZ can treat RA patients through regulating the ratio of CD4 naïve T cells, CD4 memory T cells, Th17 cells, and Treg cells in PBMC.
背景 本研究旨在探讨白细胞介素-6(IL-6)受体拮抗剂托珠单抗(TCZ)对类风湿关节炎(RA)的保护作用及其相关机制。
材料与方法 选取30例处于中重度活动期且接受长期甲氨蝶呤治疗的RA患者,每4周静脉滴注8 mg/kg/次的TCZ。在TCZ治疗前及治疗24周后采集外周血。通过密度梯度离心法收集外周血单个核细胞(PBMC)。采用流式细胞术检测PBMC中CD4初始T细胞、CD4记忆T细胞、Th17细胞及调节性T细胞(Treg细胞)的比例。评估患者的疾病活动度评分(DAS28)、C反应蛋白(CRP)、类风湿因子(RF)及抗环瓜氨酸肽抗体(CCP)水平。
结果 与治疗前相比,IL-6受体拮抗剂TCZ显著改善了患者的病情,包括DAS28评分、CRP、RF及CCP水平(P<0.01)。此外,TCZ明显上调了CD4初始T细胞比例,降低了CD4记忆T细胞比例(P<0.01)。TCZ还显著降低了Th17细胞比例,增加了Treg细胞比例(P<0.01)。
结论 TCZ可通过调节PBMC中CD4初始T细胞、CD4记忆T细胞、Th17细胞及Treg细胞的比例来治疗RA患者。