Fang S H, Hwang L H, Chen D S, Chiang B L
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei.
J Hepatol. 2000 Nov;33(5):791-8. doi: 10.1016/s0168-8278(00)80312-8.
BACKGROUNDS/AIMS: Combination IFN-a and ribavirin therapy for hepatitis C virus-infected patients has been reported to improve the response rate up to 50%. In this study, we aimed to study further the role of ribavirin in hepatitis C virus-specific immune responses.
We immunized mice with hepatitis C virus core protein with or without different concentrations of ribavirin. Forty days after immunization, hepatitis C virus-specific immune responses were followed in these mice.
We found that the mice immunized with core antigen once every 2 weeks and 0.5 mg ribavirin every day showed higher levels of core-specific IgG2 compared with those mice immunized with core antigen only. In addition, core antigen-stimulated spleen cells produced higher levels of T helper type 1 cytokines and the core-specific cytotoxic T cell activity also increased significantly. Furthermore, lipopolysaccharide-stimulated peritoneal cells produced higher levels of IL-12 in ribavirin-treated mice, and peritoneal cells isolated from naive mice also produced significantly higher level of IL-12 when cultured with ribavirin.
Ribavirin may significantly promote the T helper type 1 immune response in vivo, and, furthermore, the effect of ribavirin on IL-12 level produced by accessory cells may contribute to the T helper type 1 enhancing effect.
背景/目的：据报道，α干扰素与利巴韦林联合治疗丙型肝炎病毒感染患者可将应答率提高至50%。在本研究中，我们旨在进一步研究利巴韦林在丙型肝炎病毒特异性免疫反应中的作用。
我们用丙型肝炎病毒核心蛋白免疫小鼠，同时给予或不给予不同浓度的利巴韦林。免疫40天后，观察这些小鼠的丙型肝炎病毒特异性免疫反应。
我们发现，每2周用核心抗原免疫一次且每天给予0.5毫克利巴韦林的小鼠，与仅用核心抗原免疫的小鼠相比，其核心特异性IgG2水平更高。此外，核心抗原刺激的脾细胞产生更高水平的1型辅助性T细胞细胞因子，核心特异性细胞毒性T细胞活性也显著增加。此外，在利巴韦林处理的小鼠中，脂多糖刺激的腹腔细胞产生更高水平的白细胞介素-12，并且从未经处理的小鼠分离的腹腔细胞在用利巴韦林培养时也产生显著更高水平的白细胞介素-12。
利巴韦林可能在体内显著促进1型辅助性T细胞免疫反应，此外，利巴韦林对辅助细胞产生的白细胞介素-12水平的影响可能有助于其增强1型辅助性T细胞的作用。
