抗病毒治疗对Ⅰb型慢性丙肝患者PBMC IL-10、IL-12水平变化影响的研究

Study on effect of antiviral therapy on changes in levels of IL-10 and IL-12 secreted by PBMC in patients with genotypeⅠb chronic hepatitis C

目的研究派罗欣联合利巴韦林抗病毒治疗对Ⅰb型慢性丙肝患者外周血单个核细胞(PBMC)分泌IL-10、IL-12水平的影响,分析IL-10、IL-12水平变化与病毒学应答结果之间的相关程度,探讨IL-10、IL-12作为抗病毒疗效评价指标的可能性。方法选取血清HCV-RNA阳性的Ib型慢性丙肝患者60例,依据病毒载量将其分为3组,低病毒载量组(1.0×103IU/ml<HCV-RNA≤1.0×104IU/ml)19例、中病毒载量组(1.0×104IU/ml<HCV-RNA≤1.0×106IU/ml)23例、高病毒载量组(HCV-RNA>1.0×106IU/ml)18例,给予聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗48周,另选HCV-RNA阴性的慢性HCV感染者15例,健康献血员15例作为对照组;在抗病毒治疗前、4周、12周、48周、结束后24周取空腹静脉血,分离外周血单个核细胞,培养72小时后收集分泌物,离心取上清液,应用ELISA法检测所有研究对象的PBMC IL-10、IL-12水平。结果 HCV-RNA阳性组的慢性HCV感染者外周血PBMCIL-10水平显著高于HCV-RNA阴性组和健康献血员组,差异有统计学意义(组间F=18.67,P<0.05);三组间IL-12水平差异无统计学意义(组间F=2.15,P>0.05)。PBMC IL-10、IL-12的水平变化与病毒学应答具有相关性,应答越迅速,IL-10水平下降越明显,IL-12升高越明显。结论慢性HCV感染者细胞免疫倾向于Th2型;有效的抗病毒治疗可快速提升前炎症因子IL-12的水平,使细胞免疫方向移向Th1型;PBMC IL-10、IL-12水平变化对干扰素联合利巴韦林治疗慢性丙肝的疗效预测具有一定的参考价值。

Objective To study the changes in levels of IL - 10 and IL - 12 secreted by PBMC in patients with genotype I b chronic hepatitis C aeeepted pegylated interferon and ribavirin therapy, to analyze the correlation between changes in levels of IL - 10 and IL - 12 and response of treatment, and to study the feasibility of levels of IL - 10 and IL - 12 as indicators for evaluation of efficacy of antiviral therapy. Methods Sixty cases of ehrenic hepatitis C with genotype I b were divided into 3 groups, 19 cases in low virus load group with virus load of 1.0 × 103 IU/ml 〈 HCV - RNA ≤ 1.0 × 104 IU/ml,23 eases in medium virus load group with virus load of 1.0 × 104 IU/ml 〈 HCV - RNA ≤ 1.0 × 106 IU/ml and 18 cases in high virus load group with virus load of HCV - RNA 〉 1.0 × 106 IU/ml; and these patients were treated by combination of Pegasys and ribavirin for 48 weeks. Fifteen cases of chronic hepatitis C with negative serum HCV - RNA and 15 healthy blood donors were allocated as control groups. Peripheral blood mononuclear cells were isolated and cultured during pretherapy and different periods in therapeutic course and post - treatment, their secretions were collected after cultivation for 72 hours, and the superuatants were collected after centrifugation. Levels of PBMC IL - 10 and IL - 12 were determined by ELISA in all eases. Results The level of PBMC IL - 10 in chronic hepatitis C patients with positive HCV - RNA was significantly higher than that of control groups （ P 〈 0.05 ）. The difference in level of PBMC IL - 12 compared among three groups was not statistically significant （ P 〉 0.05 ）. The relationship between change in levels of PBMC IL - 10, IL - 12 and antiviral responses was posi- tively eorrelated, the level of PBMC IL - 10 was decreased and IL - 12 was rapidly increased while the HCV - RNA load was significantly de- clined. Conclusion Cell immunity of patients with chronic hepatitis C tends to Th2 type; the level of preinflammatory cytokines IL - 12 will be quickly increased if antiviral therapy is effective, and the direction of eell immunity will tend to Thl type; the change in levels of PBMC IL - 10 and IL - 12 has certain significance in predicting efficacy of antiviral treatment with Pegasvs and ribavirin.