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目的分析慢性乙型肝炎(CHB)患者外周血单核细胞(PBMC)干扰素-α(IFN-α)及白细胞介素18(IL-18)mRNA的诱导表达差异,评价慢性乙型肝炎患者PBMC细胞免疫功能。方法对2004年6月至2005年5月华中科技大学同济医学院附属协和医院52例门诊和住院CHB患者,聚肌胞苷酸(PolyIC)体外刺激正常对照组和CHB组患者PBMC,取培养上清利用病毒保护试验测定IFN-α2b治疗前后PBMC表达的干扰素抗病毒生物学活性。同时用脂多糖(LPS)体外刺激不同组PBMC,RT-PCR检测PBMCIL-18mR-NA水平的变化。结果治疗前干扰素治疗应答组(n=13)和无应答组(n=27)PBMC分泌的干扰素生物学活性均显著低于对照组(n=20)(均P<0.01)。应答组干扰素活性随治疗时间延长而增加,1个月时已显著高于无应答组(P<0.01);无应答组干扰素活性始终处于低下水平。治疗前,应答组和无应答组PBMCIL-18mRNA水平也显著低于对照组(均P<0.01);治疗后,应答组IL-18mRNA水平随治疗时间延长而升高,1个月时也著显高于无应答组(P<0.01),无应答组IL-18mRNA水平始终较低。PBMCIFN-α活性和IL-18mRNA水平有良好的正相关性(r=0.922,P<0.01)。结论慢性HBV感染患者的细胞免疫功能受损,不能正常表达IFN-α和IL-18,但应答组患者经干扰素治疗后表达能力逐渐恢复。
Objective To analyze the differences in the expression of interferon-α (IFN-α) and interleukin 18 (IL-18) mRNA in peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis B (CHB) Cellular immune function. Methods From June 2004 to May 2005, 52 outpatients and hospitalized patients with CHB from Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, polyims (PolyIC) stimulated PBMC in normal control group and CHB group in vitro, Determination of interferon anti-viral biological activity of PBMC expression of IFN-α2b before and after treatment with a virus protection test. Different groups of PBMCs were stimulated with lipopolysaccharide (LPS) in vitro, and the changes of IL-18 mRNA level in PBMCs were detected by RT-PCR. Results The biological activity of interferon secreted by PBMC in pretreatment IFN treatment group (n = 13) and non - response group (n = 27) were significantly lower than those in control group (n = 20) (all P <0.01). The interferon activity of response group increased with the prolongation of treatment time, which was significantly higher than that of non-response group at 1 month (P <0.01). The activity of interferon was always at a low level in non-response group. Before treatment, the level of PBMCIL-18 mRNA in response group and non-response group was also significantly lower than that in control group (all P <0.01). After treatment, the level of IL-18 mRNA in response group increased with the prolongation of treatment time, Higher than non-responders (P <0.01), non-responders IL-18 mRNA levels were consistently lower. There was a positive correlation between PBMCIFN-α activity and IL-18 mRNA level (r = 0.922, P <0.01). Conclusions Patients with chronic HBV infection have impaired cellular immunity and can not express IFN-α and IL-18 normally. However, the response of patients in the response group gradually recovered after treatment with interferon.