抗OPN抗体干预感染泡球蚴沙鼠后细胞因子水平的动态变化

Dynamic changes in cytokines from gerbils infected with Echinococcus multilocularis and treated with anti-osteopontin antibody

目的观察人工接种泡球蚴(EM)沙鼠在抗骨桥蛋白(OPN)抗体干预下体内白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、IL-5和IL-10水平动态变化,探讨抗OPN抗体对泡球蚴感染免疫机制的影响。方法采用开腹直视下肝脏穿刺注射的方法,用20%泡球蚴组织混悬液感染长爪沙鼠180只,每只0.1ml,建立肝泡球蚴病(AE)沙鼠模型。将感染沙鼠随机分为实验组、对照组和空白组,每组60只。实验组沙鼠接种泡球蚴后当天经尾静脉注射抗OPN抗体,每次0.15ml,每隔两日注射一次,注射7次后,每隔1周注射一次;对照组沙鼠经尾静脉注射兔血清(时间和剂量同上);空白组为单纯模型组。分别于感染1、20、40、60、80和100d后,各组随机选取10只沙鼠,摘眼球取血,离心,收集血清,应用酶联免疫吸附试验(ELISA)检测IL-2、TNF-α、IL-5和IL-10含量。结果感染100d时实验组IL-10为(77.93±4.13)pg/ml,对照组为(82.46±4.24)pg/ml,空白组为(84.69±5.57)pg/ml,差异有统计学意义(P<0.05),其余各时间段的IL-10水平及各时间段其他3种细胞因子水平组间比较差异无统计学意义(P>0.05)。结论 Th1细胞介导的细胞免疫与Th2细胞介导的体液免疫共同参与宿主抗肝泡球蚴免疫。抗OPN抗体可能对血清IL-10表达水平有一定的抑制作用。

Objective To observe the effects of anti-osteopontin antibody on four cytokines in gerbils infected with Echinococcus multilocularis as part of a study of the immunological mechanism by which anti-osteopontin antibody counters infection.Methods One hundred and eighty gerbils were used to create a model of hepatic alveolar echinococcosis（AE）.Gerbils were intra-abdominally injected with a 20% suspension of E.multilocularis（0.1 ml per gerbil）in the liver and the gerbils were randomly divided into an experimental group,control group,and blank group（60 gerbils per group）.Gerbils in the experimental group were injected with antibody via a tail vein when the models（0.15 ml per gerbil,with injection every three days;after the seventh injection,gerbils were injected once every other week）.Gerbils in control group were injected with serum via a tail vein（same timing and dosage） and gerbils in the blank group served as a simple model.Changes in serum levels of the cytokines IL-2,TNF-α,IL-5,and IL-10 were measured with ELISA during the infection after 1,20,40,60,80,and 100 d.Ten gerbils were randomly selected from each group.Results After 100 d,the level of IL-10 decreased in the experimental group（77.93±4.13 pg/ml） in comparison to the control group（82.46±4.24 pg/ml） and blank group（84.69±5.57 pg/ml）（P0.05）.Differences between the three groups were not statistically significant（P0.05）.Conclusion The data suggest that induction of a TH1 cell-mediated inflammatory（CMI） response with a parallel enhancement of TH2 antibody-mediated immunity（AMI） is an important mechanism by which a host defends against metacestodes.Anti-osteopontin antibody can reduce the level of IL-10 in serum.