Spanakis Nick E, Garinis George A, Alexopoulos Evangelos C, Patrinos George P, Menounos Panayotis G, Sklavounou Alexandra, Manolis Evangelos N, Gorgoulis Vassilis G, Valis Dimitrios
Medicanalysis Institute of Molecular Biology Applications, Athens, Greece.
J Clin Lab Anal. 2002;16(1):40-6. doi: 10.1002/jcla.2060.
The pathogenic role of immune-mediated mechanisms in chronic hepatitis C virus (HCV) infection has not yet been elucidated. In this study, we report different cytokine expression profiles from hemodialysis (HD) and non-HD HCV (+) patients. IL-1beta, IL-2, IL-4, IL-6, TNF-alpha, and TGF-beta1 serum levels, and liver biochemical parameters were determined in 85 individuals (41 HD patients and 44 non-HD patients). Screening for HCV RNA and anti-HCV antibodies was performed using qualitative and quantitative reverse transcription polymerase chain reaction (RT-PCR), and standardized enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) methods, respectively. IL-4 and IL-1beta demonstrated decreased serum levels in non-HD HCV carriers compared with healthy controls. Both T helper (Th) 1 and Th2 lymphocytes were highly associated with chronic HCV infection, as indicated by the increased IL-2, IL-4, and IL-6 cytokine circulating levels in all chronic active hepatitis (CAH) patients examined. An enhanced Th2 response (IL-4 and IL-6) coupled with increased TNF-alpha and IL-1beta serum levels was reported in HD HCV (-) patients. In conclusion, our data show that a virus-induced Th2 and IL-1beta immunosuppression is an early event in HCV-related chronicity. Long-term HD specifically exerts a chronic effect on IL-6, IL-1beta, and TNF-alpha serum circulating levels. Irrespective of the HD status, HCV viremia, and liver biochemistry parameters, both Th1 and Th2 responses are highly associated with chronic HCV infection.
免疫介导机制在慢性丙型肝炎病毒(HCV)感染中的致病作用尚未阐明。在本研究中,我们报告了血液透析(HD)和非HD HCV(+)患者不同的细胞因子表达谱。测定了85名个体(41名HD患者和44名非HD患者)的IL-1β、IL-2、IL-4、IL-6、TNF-α和TGF-β1血清水平以及肝脏生化参数。分别使用定性和定量逆转录聚合酶链反应(RT-PCR)、标准化酶联免疫吸附测定(ELISA)和重组免疫印迹测定(RIBA)方法进行HCV RNA和抗HCV抗体筛查。与健康对照相比,非HD HCV携带者的IL-4和IL-1β血清水平降低。在所检查的所有慢性活动性肝炎(CAH)患者中,IL-2、IL-4和IL-6细胞因子循环水平升高表明,辅助性T(Th)1和Th2淋巴细胞均与慢性HCV感染高度相关。据报告,HD HCV(-)患者的Th2反应增强(IL-4和IL-6),同时TNF-α和IL-1β血清水平升高。总之,我们的数据表明,病毒诱导的Th2和IL-1β免疫抑制是HCV相关慢性化的早期事件。长期HD对IL-6、IL-1β和TNF-α血清循环水平具有特异性慢性影响。无论HD状态、HCV病毒血症和肝脏生化参数如何,Th1和Th2反应均与慢性HCV感染高度相关。