Effects of antisense interleukin-5 gene transferred by recombinant adeno-associated virus to allergic rats.
OBJECTIVE
The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5).


METHODS
The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study.


RESULTS
The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed.


CONCLUSIONS
Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma.
Zeng
Daxiong
D
Department of Respiratory Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cao
Yong
Y
Song
Qingfeng
Q
Cao
Chao
C
Liu
Xiansheng
X
Xu
Yongjian
Y
Xiong
Weining
W
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics*; D001249:Asthma / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054413:Chemokine CCL11 / Q000097:blood / Q000276:immunology; D000229:Dependovirus; D047150:Eosinophil Cationic Protein / Q000097:blood / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics*; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection
D016375:Antisense Elements (Genetics); D054413:Chemokine CCL11; D015848:Interleukin-5; D007073:Immunoglobulin E; D010047:Ovalbumin; D047150:Eosinophil Cationic Protein