气管内应用IL-18重组腺病毒对实验性肺转移癌的治疗作用

Effect of intratracheal administration of recombinant adenovirus containing IL-18 gene in treatment of experimental lung metastasis

目的 :研究气管内应用白细胞介素 18(IL - 18)重组腺病毒 (Ad IL - 18)对实验性肺转移癌的治疗作用。方法 :(1)小鼠气管内滴入 Ad IL - 18后 ,以 RT- PCR法检测小鼠肺组织中 IL - 18m RNA表达 ,EL ISA法测定局部及外周血 IL - 18及其相关因子的水平。 (2 ) C5 7BL / 6小鼠尾静脉注射 L ewis肺癌 3L L细胞以建立肺转移癌模型 ,观察气管内应用 Ad IL - 18对实验性肺转移癌的治疗作用 ,包括肺转移结节数、动物存活期、存活率变化等 ,并比较自然杀伤 (NK )细胞和细胞毒 T淋巴细胞 (CTL )活性。 结果 :(1)气管内应用 Ad IL - 18后 6 h,小鼠肺内即可检测到 IL - 18m RNA表达 ;72 h后肺灌洗液中可测到 IL - 18,且高于外周血水平 ,而对照组肺灌洗液及外周血中均未检测到。 (2 )气管内滴入 Ad IL - 18对实验性肺转移癌有治疗作用 ,可使肺转移结节减少、动物的存活期延长及存活率升高 ,同时对 NK细胞、CTL 活性有增强作用。 结论 :气管内应用 IL- 18重组腺病毒后可有效表达 ,并对实验性肺转移癌有治疗作用。

Objective: To study the treatment of experimental lung metastasis by intratracheal injection of IL 18 gene recombinant adenovirus. Methods: (1)The mouse IL 18 mRNA was detected by RT PCR, the concentrations of IL 18, associated cytokines in lung lavage and blood were determined by ELISA at different times after intratracheal injection of IL 18 recombinant adenovirus. (2)The lung metastasis nodes, mouse survival period, survival rates were investigated in the treatment of experimental lung metastasis in C57BL/6 mouse model. The NK activity and CTL activity were determined by 51 Cr 4 h release method. Results: (1)The IL 18 mRNA could be detected in lung tissue 6 h after intratracheal use of IL 18 recombinant adenovirus, and the concentrations of IL 18 in lung lavage was higher than that of peripheral blood, and both IL 18 mRNA and IL 18 could not be detected in control groups. (2)Intratracheal use of IL 18 recombinant adenovirus had significant therapeutic effect on experimental lung metastasis with the results of increased CTL and NK activity, and with longer survival period and higher survival rates compared with the control groups. Conclusion: Intratracheal usage of adenovirus vector containing IL 18 gene has therapeutic effect on the lung metastasis, denoting that gene therapy of lung diseases can be done through airway directly with recombinant adenovirus.