[Impact of endogenous inflammation caused by adenovirus as a vector in gene therapy: experiment with mice models of acute lung injury].
OBJECTIVE
To evaluate the impact of endogenous inflammation caused by adenovirus as a vector of gene therapy on mouse model of acute lung injury (ALI).


METHODS
Black C57/B6 mice randomly divided into 4 research groups: (1) adenovirus encoded-lacZ gene treatment group (AdLacZ): n=43; (2) three control groups: (1) before 100% O2 inhalation (Con): n=26; (2) 100% O2 inhalation with TBS + PBS treatment (PBS): n=36; (3) 100% O2, inhalation without treatment (no treatment): n=33. AdLacZ reagent through intranasal administration to infect mice lungs at 48h before 100% O2 inhalation to induce ALI mouse model, which companies by mice survival rates recorded. beta-gal protein activity in lung was detected to show the level of LacZ DNA transgenic protein activity;meanwhile, the indices of lung wet/dry ratio and bronchial alveolar lavage liquid (BALF) analysis with protein concentration and cell classification were detected.


RESULTS
The method of adenovirus-mediated gene therapy with intranasal administration resulted in LacZ DNA transgenic protein activity to keep effective highly expression in lung, and the expression level maintained 2-fold increasing even after 72 h of O2 inhalation compared to that before O2 inhalation (3.688 U/mg vs. 1.589 U/mg); AdLacZ mice had more subjective to O2 inhalation compared to other groups, the 50% mice survival time of this group was shorter compared to that of the PBS group [(86 +/- 3) h vs. (94 +/- 7) h]; also in AdLacZ group, the level of nucleated cell counting in BALF was statistically higher compared to other groups at 48 h of O2 inhalation, which following with 50%-level decreased within anther 24 h O2 inhalation; on the contrary, the level of lung wet/dry ratio and protein concentration in BALF didn't show remarkably decreasing.


CONCLUSIONS
The endogenous inflammation caused by adenovirus as a vector in ALI gene therapy is temporary and rapidly weaken after getting a peak, however, enough attention still should be paid attention when evaluating the effect of gene therapy.
Wang
Yan
Y
Department of Pulmonary, Shanghai Children's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200040, China. msywang2006@yahoo.com.cn
Lu
Quan
Q
Teng
Guo-liang
GL
Sheldon
Feistein S
FS
Beers
Micheal F
MF
Fisher
Aron B
AB
D055371:Acute Lung Injury / Q000401:mortality / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D007763:Lac Operon / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D015996:Survival Rate