气管内吸入IL-12重组腺病毒对实验性肺转移癌的治疗作用

为研究气道内应用IL 12重组腺病毒 (AdIL 12 )对实验性肺转移癌的治疗作用。我们在小鼠气管内滴入AdIL 12 ,以ELISA法测定局部及外周血IL 12及相关因子水平 ,在C5 7BL/ 6小鼠尾静脉注射Lewis肺癌 3LL细胞建立肺转移癌模型 ,观察气管内应用AdIL 12对实验性肺转移癌的治疗作用 ,包括肺转移结节、动物存活期、生存率变化等 ,比较自然杀伤活性(NK )和特异性细胞毒 (CTL )活性的差异。结果显示 :(1)气管应用AdIL 12后肺灌洗液中测到IL 12 ,且浓度高于外周血水平 (P <0 0 1) ,对照组肺灌洗液及外周血中均未检出 ;(2 )气道应用AdIL 12对实验性肺转移癌有治疗作用 ,可使肺转移结节减少、动物的生存期延长及存活率升高 ,并增强了NK、CTL活性。本研究表明气道内应用AdIL 12对实验性肺转移癌有治疗作用。

Treatment of Experimental Lung Metastasis by Intratracheal Inhalation of Recombinant Adenovirus Containing IL-12 Gene

In order to study the treatment of experimental lung metastasis with recombinant adenovirus containing IL-12 gene,the reconbinant viruses were inhalated intratracheally,and the contents of IL-2 and the associated cytokines in lung lavages and blood were determined by ELISA assay in test and control groups. The therapeutic effect of this kind of virus was investigated in C57BL/6 mouse model by injecting Lewis 3LL cells of lung cancer through tail vein. The investigating items included metastatic nodes,mouse survival time and rate and the differences of activities in NK cells and specific cytotoxicity in experimental and control groups of mice. Experimental results showed that IL-12 could detected in the lung lavages in higher concentration than those in the peripheral blood 72 hours after intratracheal application of the viruses,but could not be detected in the control group. This kind of treatment could also improve the NK cell activity and cytotoxicity,reduce rate of metastatic nodes and prolong the time and rate in the experimental group. These results suggest that the gene therapy of lung cancer can be done through intratracheal inhalation of recombinant adenovirus containing IL-12 gene.