Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice

Chih Yu Hsu, H. Eugene Liu, Feei Yi Sheu, Sy Jye Leu, Bor Luen Chiang, George Hsiao, Yueh Lun Lee

研究成果: 雜誌貢獻 › 文章

11 引文 (Scopus)

摘要

Background: Asthma is a chronic disease characterized by airway inflammation caused by the dysregulated production of cytokines secreted by allergen-specific type 2 T helper (Th2) cells. Although the Th1-promoting cytokine, interleukin (IL)-12, is capable of inhibiting Th2-driven allergeninduced airway changes in mice, IL-12 also aggravates the Th1-driven inflammatory pulmonary pathology. Further, IL-10 was found to exert both anti-inflammatory and immunoregulatory activities. To avoid the sideeffects of IL-12, we hypothesized that the low-dose expression of IL-10 with concomitant IL-12 administration in the airway may represent a more effective therapy for allergic airway diseases. Thus, the present study explored the immunomodulatory and therapeutic effects of IL-10 combined with IL-12 in airway inflammation in allergic asthma. Methods: Adenovirus-expressing murine IL-10 (Ad-IL-10) and IL-12 (Ad-IL-12) were co-administrated in an established murine model of ovalbumin (OVA)-induced asthma. Results: We found that a single combined treatment of low doses of Ad-IL-10 and Ad-IL-12 efficiently inhibited the development of airway hyperresponsiveness compared to Ad-IL-10 or Ad-IL-12 treatment alone. Moreover, both Ad-IL-10 and Ad-IL-12 treatment reduced pulmonary infiltration of eosinophils and neutrophils. In addition, histological studies showed that combined treatment was able to reduce tumor necrosis factor-á-mediated airway inflammation induced by IL-12 treatment. Suppression of IL-4, IL-5, Keratinocyte-derived chemokine (KC) and eotaxin in bronchoalveolar lavage fluid was also noted in OVA-immunized mice with combined Ad-IL-10 and Ad-IL-12 treatment. Conclusions: Taken together, the results obtained in the present study indicate that co-administration of IL-12 and IL-10 may have therapeutic potential for the immunomodulatory treatment of allergic asthma.
原文英語
頁（從 - 到）11-21
頁數11
期刊Journal of Gene Medicine
卷12
發行號1
DOIs
出版狀態已發佈 - 一月 2010

指紋

Therapeutic Uses
Interleukin-12
Adenoviridae
Genetic Therapy
Interleukin-10
Inflammation
Asthma
Therapeutics
Ovalbumin
Cytokines
Lung
Th2 Cells
Neutrophil Infiltration
Interleukin-5
Bronchoalveolar Lavage Fluid
Helper-Inducer T-Lymphocytes
Eosinophils
Interleukin-4
Allergens
Chronic Disease

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery

引用此文

Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice. / Hsu, Chih Yu; Eugene Liu, H.; Sheu, Feei Yi; Leu, Sy Jye; Chiang, Bor Luen; Hsiao, George; Lee, Yueh Lun.

於: Journal of Gene Medicine, 卷 12, 編號 1, 01.2010, p. 11-21.

研究成果: 雜誌貢獻 › 文章

Hsu, CY, Eugene Liu, H, Sheu, FY, Leu, SJ, Chiang, BL, Hsiao, G & Lee, YL 2010, 'Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice', Journal of Gene Medicine, 卷 12, 編號 1, 頁 11-21. https://doi.org/10.1002/jgm.1408
Hsu CY, Eugene Liu H, Sheu FY, Leu SJ, Chiang BL, Hsiao G 等. Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice. Journal of Gene Medicine. 2010 1月;12(1):11-21. https://doi.org/10.1002/jgm.1408
Hsu, Chih Yu ; Eugene Liu, H. ; Sheu, Feei Yi ; Leu, Sy Jye ; Chiang, Bor Luen ; Hsiao, George ; Lee, Yueh Lun. / Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice. 於: Journal of Gene Medicine. 2010 ; 卷 12, 編號 1. 頁 11-21.
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abstract = "Background: Asthma is a chronic disease characterized by airway inflammation caused by the dysregulated production of cytokines secreted by allergen-specific type 2 T helper (Th2) cells. Although the Th1-promoting cytokine, interleukin (IL)-12, is capable of inhibiting Th2-driven allergeninduced airway changes in mice, IL-12 also aggravates the Th1-driven inflammatory pulmonary pathology. Further, IL-10 was found to exert both anti-inflammatory and immunoregulatory activities. To avoid the sideeffects of IL-12, we hypothesized that the low-dose expression of IL-10 with concomitant IL-12 administration in the airway may represent a more effective therapy for allergic airway diseases. Thus, the present study explored the immunomodulatory and therapeutic effects of IL-10 combined with IL-12 in airway inflammation in allergic asthma. Methods: Adenovirus-expressing murine IL-10 (Ad-IL-10) and IL-12 (Ad-IL-12) were co-administrated in an established murine model of ovalbumin (OVA)-induced asthma. Results: We found that a single combined treatment of low doses of Ad-IL-10 and Ad-IL-12 efficiently inhibited the development of airway hyperresponsiveness compared to Ad-IL-10 or Ad-IL-12 treatment alone. Moreover, both Ad-IL-10 and Ad-IL-12 treatment reduced pulmonary infiltration of eosinophils and neutrophils. In addition, histological studies showed that combined treatment was able to reduce tumor necrosis factor-{\'a}-mediated airway inflammation induced by IL-12 treatment. Suppression of IL-4, IL-5, Keratinocyte-derived chemokine (KC) and eotaxin in bronchoalveolar lavage fluid was also noted in OVA-immunized mice with combined Ad-IL-10 and Ad-IL-12 treatment. Conclusions: Taken together, the results obtained in the present study indicate that co-administration of IL-12 and IL-10 may have therapeutic potential for the immunomodulatory treatment of allergic asthma.",
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