宫内感染乙型肝炎病毒对新生儿Th1/Th2细胞的影响

The effect of intrauterine hepatitis B virus infection on type 1 and type 2 cells in neonates

目的:探讨乙型肝炎病毒(HBV)侵犯新生儿外周血单个核细胞(PBMC)后,对新生儿免疫功能的影响,了解其免疫失败发生的机理。方法:聚合酶链反应法(PCR)检测151例乙型肝炎表面抗原(HBsAg)阳性孕妇及其新生儿血清和PBMC的HBV-DNA。根据新生儿PBMC中HBV-DNA分成阴性和阳性组,将新生儿的PBMC分别在植物血凝素(PHA)和纯化HBsAg刺激下进行体外细胞培养,检测培养上清液中细胞因子干扰素γ(IFN-γ)、白细胞介素12(IL-12)、白细胞介素6(IL-6)的分泌含量。结果:①151例新生儿中,宫内感染率为37.8%(57/151)。②新生儿宫内感染组中IFN-γ、IL-12水平显著低于宫内未感染组,IL-6水平则显著高于宫内未感染组(P<0.05)。两组新生儿血清中IFN-γ与IL-12水平均呈显著正相关(P<0.01,P<0.05);IL-12与IL-6呈显著负相关(P<0.01,P<0.05);IFN-γ与IL-6亦呈显著负相关(P<0.01,P<0.05)。结论:HBV侵犯新生儿PBMC后,新生儿细胞免疫功能紊乱导致Th1型细胞因子IFN-γ、IL-12水平下降,而Th2型细胞因子IL-6水平上升,IFN-γ、IL-12抗病毒作用减弱,不利于新生儿体内HBV清除,易导致宫内感染。

Objective： To evaluate the role of infected PBMC in the intrauterine, investigate the response of cytokine in children whose mothers were HBV carriers, understand the mechanism and the prognosis of immune failure. Methods： HBV - DNA in plasma and PBMC from mothers who＇s HBsAg positive and their neonates were examined by PCR. According to HBV - DNA in PBMC of neonates, they were divided into two groups. The PBMC isolated from neonates were cultured with purified HBsAg or PHA. The levels of supernatant interleukin -6, interleukin -12 and Interferon -γ were measured by enzyme linked immunosorbent assay （ELISA）. The correlation risk factors were analyzed. Results： 57 cases （37. 8% ） of 151 neonates whose mothers were HBsAg positive infected HBV. The IFN - γ, IL - 12 levels of the neonates with intrauterine infection were significantly lower than those without intrauterine infection and control group （ P 〈 0. 05 ）, IL -6 levels were contrary to IFN -γ and IL - 12 （P 〈 0. 05 ） . The positive correlation existed between IFN - 3, and IL - 12 levels （P 〈 0. 05） . IL - 12 and IL -6 levels were negatively correlated, and so were IFN - γand IL -6 levels （P 〈 0. 05 ） . Conclusion： There are imbalance of Thl/Th2 cells in pregnant women, which cause IFN -γ and IL - 12 activities decrease, and the activity of IL -6 increases. Thus the antiviral responses of IFN -γ and IL- 12 are inhibited, resulting higher incidence of intrauterine infection.