拉米夫定对慢性乙型肝炎血清IFN-γ和IL-10水平的影响

目的探讨拉米夫定治疗对慢性乙型肝炎患者血清IFN-γ和IL-10水平的影响及临床意义。方法根据患者对拉米夫定治疗12个月后不同应答情况分组进行回顾性研究,利用双抗体夹心ELISA法检测治疗前后不同时相点血清IFN-γ、IL-10水平,以与正常对照校对后的IFN-γ/IL-10比值作为Th1/Th2平衡指标,健康献血员作对照。结果HBeAg阳性完全应答组治疗前IFN-γ水平高于部分应答组,治疗后可见IFN-γ水平升高、IL-10水平降低,Th1/Th2平衡得以恢复并保持Th1优势应答;HBeAg阳性部分应答组和HBeAg阴性组治疗后IFN-γ和IL-10水平变化不大,Th1/Th2平衡仍以Th2为优势;YMDD变异后血清IFN-γ水平降低,血清IL-10水平升高。结论拉米夫定应答程度与治疗前血清IFN-γ水平有关;治疗后Th平衡的恢复是完全应答实现的保证;Th平衡可以作为HBeAg阴性慢性乙型肝炎患者血清免疫学应答的评价指标,YMDD变异对机体抗HBV免疫有一定的影响。

Changes and significance of sera levels of IFN-γ and IL-10 in chronic hepatitis B patients following lamivudine

Objective To explore the changes and signficance of sera levels of IFN-γ and IL-10 in chronic hepatitis B(CHB)patients before and after lamivudine therapy.Methods According to the different response to lamivudine therapy, and the retrospective study was developed. Sera were collected from patients with chronic hepatitis B before and after lamivudine therapy ,and from healthy blood donors. Then sera IFN-γ and IL-10 levels were measured by ELASA method. The ratio of IFN-γ/IL-10 was selected as the marker of Th1/Th2 balance after checked by normal control. Result Sera level of IFN-γ was higher in HBeAg positive and complete response group than HBeAg positive and non-complete(i.e partial) response group before therapy. After treatment, IFN-γ level was higher, and IL-10 level was lower and the tendency of Th1/Th2 balance was to Th1 direction in HBeAg positive and complete response group. Sera levels of IFN-γ and IL-10 in HBeAg positive and non-complete response group and HBeAg negative group and the tendency of Th1 direction had no obvious changes, still Th2 was dominant. After YMDD motif mutant, the level of IFN-γ declined, but was higher than bottom level of pre-therapy and IL-10 increased. Conclusion Anti-virus immune response of CHB patients can be recovered after lamivudine therapy. The degree of response is related to sera level of IFN-γ pre- and post- therapy. Recovery of Th balance after therapy assures complete response. Th1/Th2 balance may be the marker of serum immunity response of HBeAg negative CHB patient after lamivudine therapy. After YMDD motif variation, the immune pressure to HBV can keep. There is hidden opportunity to induce active hepatitis after YMDD motif mutant.