目的了解日本血吸虫感染小鼠体内Th1/Th2反应动态变化,评价Th细胞反应与肉芽肿病理改变之间的相关性。方法C57BI。/6小鼠感染日本血吸虫后4、6、8、12周,分别检测其血清中IFN-γ、IL4、IL~13水平,脾细胞中Th1/Th2比例,观察感染小鼠肝脏虫卵肉芽肿的形成和发展趋势,并评价各个细胞因子与虫卯肉芽肿大小之间的相关性。统计分析采用非参数秩和检验和Spearman秩相关分析。结果日本血吸虫感染后第4周,小鼠血清IFN了浓度为(2.835±0.049)lgpg/mL,显著高于对照组的(1.787±0.174)lgpg/mL(Z=-2.646,P=0.008);第6周起,小鼠血清IFN-γ浓度开始逐渐降低,但直至感染12周时仍显著高于对照组(Z=-2.457,P=0.014)。血清中IL-4(Z=-2.646,P=0.008)和IL-13(Z=-2.646,P=0.008)水平从感染6周始升高,于第8周达高峰。经可溶性虫卵抗原(SEA)刺激后,脾脏中Thl/TE2比例于感染8周时为0.5(95%可信区间0.2~1.2),12周时为0.3(95%可信区间0.3~0.6),均显著低于对照组(Z=2.173,P=0.030;z=2.551,P=0.011)。与未经SEA刺激的脾细胞相比,经SEA刺激的脾细胞Th1/Th2比例在感染第8周(Z=2.236,P=0.025)和第12周(Z=3.130,P=0.002)均显著降低。感染6周时,小鼠肝脏中开始出现大量虫卵肉芽肿,其直径随感染进展逐渐增大。相关性分析发现,感染12周时血清IL-13水平与肝脏虫卵肉芽肿直径之间存在显著负相关(r=-0.636,P-0.048)。结论血吸虫感染早期Th1反应占优势,随着血吸虫成熟并开始产卵,Th1反应逐渐减弱,而出现Th2反应极化现象。Th2反应可能在肉芽肿纤维化过程中发挥作用。
Objective To investigate the dynamic changes of T helper (Th) responses and hepatic granuloma development during Schistosoma )aponicum infection and to evaluate the possible correlation between the Th1/Th2 eytokines and pathological liver damage. Methods Sera from both Schistosoma japonicum infected C57BL/6 mice and uninfected controls were measured for interferon- gamma (IFN-y), interleukin (IL)-4 and IL-13 at week 4, 6, 8 and 12 post-infection. At the same time, the splenic Thl/Th2 ratio was examined. The development of liver granulomas in infected mice was also observed and the correlation between the cytokines and granulomas were assessed. Wilcoxon test and Spearman rank correlation test were performed for data analysis. Results Serum IFN γ level in infected mice was (2. 835±0. 049) lgpg/mL at week 4 post infection, which was significantly higher than that in controls [(1. 787±0. 174) lgpg/mL,Z=2. 646, P=0. 0081. Thereafter, the level declined after week 6, but remained higher than controls at the end of 12-week experiment (Z= 2. 457, P=0.014). IL-4 and 1L-13 levels did not increase until week 6 (Z=2. 646,P=0.008; Z=2.646,P=0.008), and peaked at week 8. After soluble egg antigen (SEA) stimulation, splenic Thl/Th2 ratio in infected mice was 0.5 (95% CI 0. 2--1.2) at week 8 and 0.3 (95% CI 0. 3--0.6) at week 12 post infection, both of which were significantly lower than those in uninfected controls (week 8: Z=2. 173, P 0. 030; week 12:Z=2.551, P=0. 011). Compared with unstimulated splenic cells, splenic Th1/Th2 ratio after SEA stimulation significantly decreased at week 8 (Z=2. 236, P=0.025) and week 12 (Z=3.130, P 0.002). Granulomaswere first observed in livers at week 6 and the size kept on increasing. A negative correlation between serum IL-13 and the diameter of liver granulomas was discovered at week 12 post infection (r=-0. 636, P 0. 048). Conclusions Thl response is dominant during the early stage of Schistosoma japonicum infection. However