来氟米特对类风湿关节炎患者外周血Th1/Th2平衡和关节功能的影响

Effect of leflunomide on Th1/Th2 balance in the peripheral blood and joint function of patients with rheumatoid arthritis

目的:探讨来氟米特对类风湿关节炎(rheumatoidarthrtitis,RA)患者外周血T淋巴细胞亚群和关节功能的影响及其可能的作用机制。方法:收集25例RA患者(RA组)和10例接受来氟米特治疗前及治疗3个月后的RA患者(治疗组)的外周血,对CD4+,CD8+细胞分泌白细胞介素-4(IL-4)和γ干扰素的情况进行检测。选择9例健康志愿者作为对照组。采用细胞内细胞因子染色、三色流式细胞分析法检测单个细胞分泌细胞因子的情况。结果:RA患者和健康对照组的外周血CD4+/CD8+T淋巴细胞中,分泌(干扰素的细胞群均比分泌IL-4的细胞群多(t=3.534,P<0.01),同健康对照组犤(7.61±3.27)%犦比较,RA组患者外周血中Th1型细胞犤(4.57±2.70)%犦明显减少(t=-2.233,P<0.05)。接受来氟米特治疗后产生γ干扰素的Th1型、Tc1型细胞和产IL-4的Th2型细胞明显减少(分别t=3.709,3.419,3.211,均P<0.01),而Tc2型细胞则无明显增加或减少(t=1.022,P<0.05),各项关节功能指标包括关节肿胀指数、血沉、C-反应蛋白等均显著下降(t=3.466,3.325,3.207,均P<0.01)。结论:氟米特可能通过抑制Th1型和Tc1型的分化、减少Th1/Tc1型细胞因子如γ干扰素的分泌而发挥抗炎和改善关节功能的作用。

AIM:To investigate the effect and possible functional mechanism of leflunomide on T lymphocyte subsets in peripheral blood and joint function in patients with rheumatoid arthritis (RA). METHODS:Peripheral blood was selected from 25 RA patients (RA group) and 10 patients who had received leflunomide before treatment and 3 months after treatment(treatment group) respectively. Interleukin 4 (IL 4) and interferon γ(IFN γ) status of CD4+, CD8+ were measured. Nine healthy volunteers were chosen in control group. Cell factors selected from single cells were measured by trichromatic flow cytometry method. RESULTS:Cell population excreting IFN γ was more than that excreting IL 4 in CD4+ / CD8+ in both RA group and control group (t=3.534,P< 0.01), and compared with the control group [(7.61±3.27)%], Th1 and Tc1 cells [(4.57±2.70)%] in peripheral blood were significantly decreased in the RA group (t=2.233,P< 0.05). Th1 and Tc1 cells which produced IFN γ and Th2 cells which produced IL 4 after leflunomide treatment were remarkably decreased (t=3.7.9, 3.149, 3.211, respectively, all P< 0.01), while no obvious change was found in Tc2 cells (t=1.022, P< 0.05). Joint function indexes, including swelling of joint index, erythrocyte sedimentation, C reactive protein, etc. all significantly decreased (t=3.466, 3.325, 3.207, all P< 0.01). CONCLUSION:The anti inflammatory effect and joint function amelioration of leflunomide may be related to the prevention of Th1/Tc1 differentiation and the decrease of the excretion of Th1/Tc1 cytokines as IFN γ.