慢性丙型肝炎和肝硬化患者外周血Th17和Treg细胞及其相关细胞因子水平变化

Changes of peripheral blood Th17 and Treg cells and their related serum cytokines in patients with chronic hepatitis C and liver cirrhosis

目的调查慢性丙型肝炎(CHC)和丙型肝炎肝硬化(LC)患者外周血辅助性T淋巴细胞17(Th17)、调节性T淋巴细胞(Treg)及其相关细胞因子水平的变化。方法 2014年10月~2016年10月本院收治的CHC患者33例,丙型肝炎肝硬化患者27例和健康体检者30例。给予CHC患者α-干扰素联合利巴韦林(PR)方案治疗12 m。采用ELISA法检测白介素-6(IL-6)、IL-10、IL-17和转化生长因子-β(TGF-β),使用流式细胞仪检测外周血Th17和CD4+CD25+Foxp3+Treg细胞数。结果 LC和CHC患者外周血Th17和Treg细胞比率和Th17/Treg比值分别为(4.6±0.7)%、(2.7±0.5)%和(1.6±0.4),和(5.8±0.9)%、(3.1±0.6)%和(1.9±0.5),均显著高于健康人[(2.3±0.4)%、(1.7±0.4)%和(1.4±0.2),P<0.05],LC患者外周血Th17和Treg细胞比率和Th17/Treg比值显著高于CHC患者(P<0.05);LC和CHC患者血清IL-6、IL-10、IL-17和TGF-β水平分别为(9.9±2.5)ng/L、(18.0±3.2)ng/L、(15.3±2.8)ng/L和(5.5±0.8)ng/L,和(14.1±3.0)ng/L、(21.4±4.0)ng/L、(23.3±3.9)ng/L和(7.2±1.2)ng/L,显著高于健康人[(6.7±1.1)ng/L、(14.2±2.9)ng/L、(5.3±0.6)ng/L和(4.3±1.0)ng/L,P<0.05],LC患者血清IL-6、IL-10、IL-17和TGF-β水平显著高于CHC患者(P<0.05);CHC患者治疗后外周血Th17和Treg细胞比率及血清TGF-β、IL-10和IL-17水平分别为(3.4±0.6)%、(1.9±0.4)%、(4.7±0.6)ng/L、(15.1±2.5)ng/L和(11.5±2.1)ng/L,均显著低于治疗前,差异有统计学意义(t=7.477、t=7.177、t=4.596、t=4.102、t=6.237,P<0.05)。结论 CHC和丙型肝炎肝硬化患者外周血Th17和Treg细胞比率增高,相关细胞因子水平也升高,可能参与了丙型肝炎病毒感染的发病过程,在抗病毒治疗后血清细胞因子水平降低,可能有助于对疗效的观察。

Objective To investigate the changes of peripheral blood Th17 and Treg cells and their related serum cytokines in patients with chronic hepatitis C（CHC） and liver cirrhosis（LC）.Methods 33 patients with CHC,27 with CHC-induced LC patients and 30 healthy persons were recruited in this study between October 2014 and October 2016.The patients with CHC received PR therapy for 12 months.The percentages of peripheral blood Th17 and CD4＋CD25＋Foxp3＋Treg cells and serum interleukin-6（IL-6）,IL-10,IL-17 and transforming growth factor-β（TGF-β） were detected by FCM and ELISA respectively.Results The percentages of Th17 and Treg cells and the Th17/Treg ratio in patients with LC were（4.6±0.7）%,（2.7±0.5）% and（1.6±0.4）,and in patients with CHC were（5.8±0.9）%,（3.1±0.6）% and（1.9±0.5）,both significantly higher than（2.3±0.4）%,（1.7±0.4）% and（1.4±0.2） in healthy control（P〈0.05）,and the percentages of Th17 and Treg cells and the Th17/Treg ratio in patients with LC were significantly higher than those in patients with CHC（P〈0.05）;serum levels of IL-6,IL-10,IL-17 and TGF-beta in patients with LC were（9.9±2.5） ng/L,（18.0±3.2） ng/L,（15.3±2.8） ng/L and（5.5±0.8） ng/L and in patients with CHC were（14.1±3.0） ng/L,（21.4±4.0）ng/L,（23.3±3.9） ng/L and（7.2±1.2） ng/L,both significantly higher than（6.7±1.1） ng/L,（14.2±2.9） ng/L,（5.3±0.6） ng/L and（4.3 ±1.0） ng/L in healthy persons（P〈 0.05）,and serum IL-6,IL-10,IL-17 and TGF-β levels in patients with LC were significantly higher than those in patients with CHC（P 〈0.05）;the percentages of Th17 and Treg cells,and serum TGF-β,IL-10 and IL-17 levels in patients with CHC at the end of the treatment weere（3.4 ±0.6）% and（1.9±0.4）%,and（4.7±0.6） ng/L,（15.1±2.5） ng/L and（11.5±2.1） ng/L,all significantly lower than those before treatment（t=7.477,t=7.177,t=4.596,t=4.102,t=6.237,P〈0.05）.Conclusion The blood Th17 and Treg cell numbers and their related serum cytokines in patients with CHC and LC increase,which might be closely related to the pathogenesis of hepatitis C viral infection.The surveillance of the regulatory T lymphocytes and cytokines might be helpful in evaluating antiviral therapy.