胸腺五肽显著增强干扰素在抗病毒治程中的特异性CTL效应

Thymopentin 5 Significantly Enhanced the HBV-specific CTL Reactivity in Interferon Antiviral Therapy

目的:探究在e抗原(HBe Ag)阳性的慢性乙型肝炎患者采用聚乙二醇干扰素-2a(peg-2a)联合核苷类药物治疗过程中,加用胸腺五肽对细胞免疫应答的影响。方法:选择采用聚乙二醇干扰素α-2a联合核苷类药物(拉米夫定+阿德福韦酯)治疗48周,HBe Ag仍为阳性,且HLA-A2阳性的慢性乙型肝炎患者18例,分为两组。一组原方案延长联合治疗作为对照,另一组在原方案基础上再加用胸腺五肽治疗(10 mg/次,2次/周,共24周)治疗,所有病人均治疗至96周。并做体外HBV特异性细胞毒T淋巴细胞(HBV specific CTL)培养增殖,通过Elispot技术分析其分泌细胞因子(肿瘤坏死因子-α,干扰素-γ,白介素-10)的功能。结果:HBe Ag转阴率,治疗96周时联合胸腺五肽组为44.4%(4/9),原方案对照组为22.2%(2/9)。HBs Ag滴度,48周时,HBs Ag为4571±3772 IU/m:;96周时,联合胸腺五肽组为1962±2869 IU/m L,转阴1人,原方案对照组为3490±3124 IU/m L,P=0.093。HBV特异性CTL培养增殖,96周时联合胸腺五肽组高于原方案对照组,且联合胸腺五肽组TNF-的分泌也高于原方案对照组,P<0.05。结论:胸腺五肽显著增强干扰素抗病毒治疗过程中的特异性CTL效应。

Objective： To investigate whether Thymopentin 5 （TP5） affects cellular immune during interferon antiviral therapy in HBeAg-positive chronic hepatitis B patients. Methods： 18 patients didn＇t achieve HBeAg seroconversion after peginterferon α-2a com- bined with lamivudine and adefovir dipivoxil for 48 weeks. They were randomly divided into two groups including continuing interferon based combination therapy with （n=9） or without （n=9） TP5 （10 mg, twice a week for 24 weeks） till 96 weeks. We conduct in vitro HBV specific CTL cultures and proliferation assays, HBcAg-induced cytokine secretion （INF-γ, TNF-α, 1L-10）. Results： In TP5 administrated group, the rate of HBeAg seroconversion was 44.4 % （4/9）, mean HBsAg level was 1962±2869 IU/mL. In control group, the rate of HBeAg seroconversion was 22.2 % （2/9）, mean HBsAg level was 3490＋ 3124 IU/mL. Proliferative response of HBV specific CTL in TP5 administrated group was relatively strong at week 96. TNF-α production also increased at week 96 in TP5 administrated group, as com- pared to control group. Conclusions： Thymopentin 5 significantly enhanced the HBV-specific CTL reactivity in interferon antiviral therapy.