Immunological response to interferon-γ priming prior to interferon-α treatment in refractory chronic hepatitis C in relation to viral clearance
Immunological response to interferon-γ priming prior to interferon-α treatment in refractory chronic hepatitis C in relation to viral clearance
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DOI：
10.1046/j.1365-2893.2001.00274.x
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发表时间：
2001-05-01
影响因子：
2.5
通讯作者：
Hayashi, N
中科院分区：
文献类型：
--
作者：
Katayama, K;Kasahara, A;Hayashi, N
本研究的目的是阐明难治性慢性丙型肝炎患者在开始α-干扰素治疗前预先给予γ-干扰素的免疫学和病毒学应答。入选了22名对6个月IFN-α治疗无应答者。HCV基因型均为Ib型。每天施用天然IFN-γ（1 MIU/天）持续14天，随后每天施用天然IFN-α（5 MIU/天）持续14天，然后每周施用三次持续22周。测定血清免疫学参数（IL-10、新蝶呤、BMG、sCD 8、sCD 4、IL-6、IL-12）以及几种细胞因子（IFN-γ、TNF-α、IL-2、IL-4、IL-5、IL-6、IL-10）的水平。三名患者退出;两名是因为其他疾病的发生，一名是因为不良反应。在IFN-α治疗期结束时，19名患者中有6名HCV-RNA变为阴性（治疗结束反应; ETR）。IFN给药完成后6个月，19例患者中有2例出现病毒学持续应答（SR）。治疗开始后6周，平均血清IL-10水平显著降低。其他免疫学参数水平在IFN-γ给药期间显著增加，并且在IFN-α给药开始后趋于恢复到治疗前水平。单变量逻辑回归分析表明，这些参数水平的初始变化或Th 1/Th 2参数水平比值的变化是指示治疗反应结束的有用因素。这些发现表明，在难治性慢性丙型肝炎患者开始IFN-α治疗之前，用TNF-γ引发可以调节宿主免疫应答，这可能有助于病毒清除。
The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with TFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.