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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)11-21
Number of pages11
JournalJournal of Gene Medicine
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Keywords

  • Adenoviral vector
  • Airway inflammation
  • Asthma
  • Interleukin-10
  • Interleukin-12

ASJC Scopus subject areas

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

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