GM-CSF治疗HBV宫内感染婴儿的临床作用及对血清Thl/Th2类细胞因子的影响

Effects of GM-CSF on intrauterine hepatitis B virus infected infants and the serum Thl/Th2 balance

【目的】初步观察重组粒细胞-巨噬细胞集落刺激因子(granulocyte-monocyte colony stimulating factor,GM-CSF)作为酵母重组乙型肝炎疫苗(rHBvac)的佐剂对HBV宫内感染婴儿治疗临床作用及对血清Thl/Th2细胞因子的影响。【方法】新生儿出生时及1个月龄检查乙肝五项HBsAg(+)和HBV DNA>1 000copy/mL者分为两组:治疗组20例,新生儿出生后给予乙肝疫苗10μg三角肌肉注射(疫苗注射时间按0、1、6方案),乙肝免疫球蛋白200U臀部肌肉注射,20d1次,共3次,注射乙肝疫苗后3d同一部位皮内注射GM-CSF 10μg/kg。对照组20例,乙肝疫苗10μg三角肌肉注射(0、1、6方案),乙肝免疫球蛋白200U臀部肌肉注射,20d1次,共3次。1岁时抽外周静脉血检测乙肝五项、HBV DNA的变化及血清IL-4和IFN-γ水平。【结果】治疗组7个月婴儿HBsAg转阴率25%(5/20),对照组7个月婴儿转阴率为5%(1/20),两组比较差异无统计学意义(P>0.05);治疗组IFN-γ水平高于对照组,两组比较差异有统计学意义(P<0.01),IL-4水平两组比较差异无统计学意义(P>0.05)。【结论】GM-CSF联合乙肝疫苗及乙肝免疫球蛋白可提高HBV宫内感染儿HBsAg转阴率,并调节Th1/Th2细胞因子平衡,对HBV宫内感染儿有一定的治疗作用。

[Objective] To investigate the effects of granulocyte-macrophage colony stimulating factor（GM-CSF） on intrauterine hepatitis B virus （HBV） infected infants and the serum Thl/Th2 balance. [Methods] Forty intrauterine in- fected infants entered the study. They were randomized into two groups. Twenty babies were assigned to GM-CSF group and received combined therapy with 10 μg of rHBvac and 200 U HBIG injected intramuscularly at different sites, 10 μg/kg of GM-CSF intradermally after three days at receiving rHBvac the same point. Twenty babies were assigned to control group and receiving 200 U HBIG and 10 μg intramuscular rHBvac injections at different sites. One year after birth,the post-treat- ment serum samples were collected to test HBV-DNA quantification and other HBV serological markers with the baseline samples at the same time. Levels of interferon-gamma （IFN-γ） and interleukin （IL）-4 in blood serum in spontaneous and su peruatant were measured by enzyme-linked immunosorbent assay（ELISA）. [Results] All subjects completed the three - dose schedule,no adverse events were reported in either group. After the treatment, 5 children became HBsAg and HBV DNA negative in GM-CSF group, however the difference did not reach to a significant level;One children became HBsAg and HBV DNA negative in control group. The IFN-γ levels of GM-CSF group were significantly higher than those of control group（P〈0.01）. There was no significant diference in IL-4 levels among the two groups （P〈0.05）. [Conclusion] Combined GM-CSF,rHBvac and HBIG therapy have some use in intrauterine infected infants who are not protected by im- munoprophylaxis.