IL-12对干扰素α治疗的慢性乙型肝炎患者外周血单个核细胞产生细胞因子的影响

目的探讨干扰素α治疗慢性乙型肝炎过程中IL-12对其外周血单个核细胞(PBMC)产生IFNγ和IL-10的动态影响. 方法用ELISA法分别检测20例慢性乙型肝炎患者在干扰素α2b治疗前、治疗3个月、治疗6个月时PBMC在PHA(100μg/ml)、HBcAg(1μg/ml)、HBeAg(1μg/ml)单独或联合IL-12(10ng/ml)体外培养48h后培养上清液INFγ和IL-10的水平. 结果 12例干扰素应答患者联合IL-12诱导,同一诱导组在治疗3个月和6个月同治疗前比较,IFNγ水平明显增高(P＜0.01),同一治疗阶段,单独抗原诱导和联合IL-12诱导相比,联合诱导组IFNγ水平明显增高(P＜0.01),治疗3个月和6个月时,IL-12对IL-10的产生表现出明显的抑制作用(HBcAg诱导组例外).8例干扰素无应答患者联合IL-12诱导,同一诱导组在治疗3个月和6个月同治疗前相比,IFNγ水平明显增高(P＜0.01),同一治疗阶段,单独抗原诱导和联合IL-12诱导相比,联合诱导组IFNγ水平明显增高,并随治疗时间的延长,协同效应更为明显. 结论在干扰素治疗过程中,IL-12对乙型肝炎患者PBMC产生IFNγ表现明显的协同效应,特别对无应答患者产生IFNγ协同效应时间明显缩短,提示IL-12 联合干扰素α可能提高干扰素α治疗慢性乙型肝炎的疗效.

Effect of IL-12 on IFNγ and IL-10 produced by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection during IFNα treatment

OBJECTIVE: To investigate the effect of IL-12 on IFN-gamma and IL-10 production of peripheral blood mononuclear cells (PBMC) in chronic hepatitis B virus infection patients during IFN-alpha treatment. METHODS: Before and after IFN-alpha treatment of 3 months and 6 months, PBMC of 20 patients with chronic hepatitis B virus infection were collected and cultured in vitro in the culture fluid containing PHA (100 microg/ml), HBcAg (1 microg/ml), or HBeAg (1 microg/ml) for 48 h under the condition of the presence or absence of IL-12 (10 ng/ml). Then the levels of IFN-gamma and IL-10 were determined by ELISA. RESULTS: There were 12 responders and 8 nonresponders to IFN-alpha treatment. In the responders, the enhancing effect of IL-12 on IFN-gamma production was significantly greater after IFN-alpha treatment than before the treatment. The production of IL-10 was suppressed in the presence of IL-12 after 3 months and 6 months of IFN-alpha treatment. In the same treatment time, the level of IFN-gamma in the presence of IL-12 was significantly higher than that in the absence of IL-12. To the nonresponders, the enhancing effect of IL-12 on IFN-gamma production was also significantly increased after IFN-alpha treatment. Moreover, in the same treatment time, the level of IFN-gamma in the presence of IL-12 was significantly higher than that in the absence of IL-12. CONCLUSIONS: The enhancing effect of IL-12 on IFN-gamma production of PBMC in patients with chronic hepatitis B virus infection is increased during IFN-alpha treatment. IFN-alpha and IL-12 may enhance the efficacy for the treatment of chronic hepatitis B virus infection.