IL-12~＋重组卡介苗降低哮喘小鼠气道炎症的作用及其机制研究  

Impact of recombinant IL-12^+ balillus calmette-guerin vaccination on airway inflammation in murine asthma model and its mechanism

作　　者：罗艳 刘恩梅[2] 邓昱[2] 王莉佳[3] 臧娜 谢晓虹[2] 倪科 李思敏 符州[2] 杨锡强[2] 

机构地区：[1]儿科学重庆市重点实验室重庆市儿童发育重大疾病诊治与预防国际合作基地,400014 [2]重庆医科大学附属医院呼吸中心,400014 [3]儿童发育疾病研究省部共建教育部重点实验室,重庆400014

出　　处：《免疫学杂志》2011年第12期1043-1047,共5页Immunological Journal

基　　金：国家自然基金资助项目(NSFC 30972698)

摘　　要：目的探讨IL-12+重组卡介苗(recombinant balillus calmette-guerin secreting IL-12,rBCG)新生期接种对实验性哮喘小鼠气道炎症和气道高反应(airway hyperresponsiveness,AHR)的作用及其可能机制。方法新生Balb/c小鼠分4组:对照组(control组),卵白蛋白(OVA)组,rBCG干预(rBCG/OVA)组,rBCG/OVA/IFN-gamma中和抗体(rBCG/OVA/anti-IFN-gamma Ab)组。除对照组外,其余3组均给予OVA致敏和激发。最后一次激发后测24 h内AHR,观察支气管肺泡灌洗液(bronchoalveolarlavage fluid,BALF)中细胞总数及分类,评估肺部炎症变化程度,采用酶联免疫吸附双抗体夹心法(ELISA)检测BALF中IFN-gamma、IL-10水平。结果 1)OVA组BALF中细胞总数、嗜酸性粒细胞、中性粒细胞、淋巴细胞绝对计数和炎症病理评分均明显高于对照组,rBCG/OVA组上述内容均显著低于OVA组。2)新生期rBCG接种能显著降低哮喘小鼠模型的气道高反应性。3)rBCG/OVA组支气管肺泡灌洗液中IFN-gamma、IL-10水平明显高于OVA组。4)rBCG/OVA组与接种rBCG同时并使用anti-IFN-gamma Ab的哮喘小鼠相比气道炎症和AHR无显著差异。结论新生期rBCG接种能抑制哮喘小鼠气道炎症和AHR,促进IFN-gamma和IL-10的产生,其抗哮喘效应可能与其促进IL-10分泌有关。To explore the impact of recombinant IL-12＋ balillus calmette-guerin secreting（rBCG） vaccination on airway inflammation and airway hyper-responsiveness in murine asthma model,neonatal Balb/c mouse were divided into four groups： control,OVA,rBCG/OVA,rBCG/OVA/anti-IFN-gamma Ab groups.Except the control group,the mice of the other three groups were sensitized and undergone OVA challenge.Cell count in bronchoalveolar lavage fluid（BALF）,score inflammatory characteristics of lung sections,cytokines IL-10 and IFN-gamma in BALF by ELISA,Airway hyper-responsiveness（AHR） in 24 h after the last OVA challenge were detected.The results showed that the number of total cells,eosinophils,neutrophils,lymphocytes,score inflammatory characteristics of lung sections and AHR were increased in OVA groups compared with those in control groups,however,all of those were decreased in rBCG/OVA group.The rBCG/OVA groups had significantly higher IL-10 and IFN-gamma levels in BALF as compared with OVA groups.There was no significant difference in airway inflammation and AHR between rBCG/OVA groups and neonatal rBCG vaccinated mice treated with anti-IFN-gamma Ab.Thus,we concluded that neonatal rBCG vaccination could significantly reduce AHR and inflammatory of lung,and the mechanism of anti-asthma effects of neonatal rBCG vaccination might be associated with IL-10 in murine asthma model.

关 键 词：哮喘 IL-10 IFN-GAMMA 

分 类 号：R392.31[医药卫生—免疫学]