慢性丙型肝炎患者外周血单个核细胞中趋化因子水平与干扰素治疗的关系

Alterations in chemokine expression in PBMC following HCV chronic infection and it′s association with IFN treatment

目的了解丙型肝炎病毒(HCV)慢性感染患者外周血单个核细胞(PBMC)中趋化因子mRNA表达水平及与α干扰素(IFNα)治疗的关系。方法以实时反转录聚合酶链反应(realtimeRTPCR)法动态观察35例慢性丙型肝炎患者接受IFN联合利巴韦林治疗前、治疗3个月、6个月后其外周血单个核细胞中白细胞介素8(IL8)、T细胞活化蛋白3(TCA3/I309)、γ干扰素诱生的单核因子(MIG)、胸腺及活化调节趋化因子(TRAC)和巨噬细胞源性趋化因子(MDC)的mRNA表达水平。结果治疗前慢性丙型肝炎患者IL8、MIG、TARC和I309的mRNA表达水平均高于正常对照组(n=12),差异有统计学意义(P<0.05或P<0.001)。治疗过程中IL8、MIG、TARC的表达水平有显著下降。治疗前的IL8、MIG和MDC的表达水平在HCV高复制组(HCVRNA>106copies/ml,n=21)和HCV低复制组(HCVRNA<106copies/ml,n=14)之间差异有统计学意义(P<0.05),高复制组的表达水平明显高于低复制组。然而上述5个趋化因子的治疗前表达水平在丙氨酸转氨酶(ALT)异常组(n=24)和ALT正常组(n=11)之间差异无统计学意义,与干扰素疗效和病毒基因型也无相关性(P>0.05)。结论HCV慢性感染能诱导外周血单个核细胞表达IL8、I309、MIG和TARC。IFN控制感染后,IL8、MIG和TARC的表达下降。治疗前的上述趋化因子表达水平与干扰素疗效和肝组织的炎症损伤程度无直接相关性。

Objective To study the mRNA levels of chemokines in the patients with chronichepatitis C and it′s association with IFN therapy. Methods The mRNA levels of IL-8, T cell activation protein-3 (TCA-3 or I-309), monokine induced by interferon γ(MIG), thymus and activation-regulated chemokine (TRAC) and macrophage-derived chemokine (MDC) in peripheral blood mononuclear cells (PBMC) of chronic hepatitis C patients were determined by real-time RT-PCR before and during the IFN-α therapy. The ratio of chemokine/GAPDH was regarded as the relative expression level of chemokine. Results The mRNA levels of IL-8, I-309 and MIG in peripheral blood of the patients were significantly higher in patients with chronic hepatitis C than those in healthy donors (P<0.05 or P<0.001). During the treatment, the mRNA levels of IL-8, MIG and TARC obviously decreased. Additionally, the expressive levels of IL-8, MIG and MDC in the high HCV loading group (HCV RNA>106 copies/ml, n=21) were much higher than those in the low HCV loading group (HCV RNA<106 copies/ml, n=14). However, the mRNA levels of these five chemokines before treatment were not correlated with serum ALT level, HCV genotype or the outcome of IFN-α therapy. Conclusion Chronic infection of HCV up-regulates the mRNA expression of IL-8, I-309, MIG and TARC in PBMC. Among them, IL-8, MIG and TARC decreases after IFN treatment. The levels of these chemokines before treatment can′t used to predict the outcome of IFN therapy and is not correlated with the severity of inflammation.