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Synergistic therapeutic effects of combined adenovirus‐mediated interleukin‐10 and interleukin‐12 gene therapy on airway inflammation in asthmatic mice
Author(s) -
Hsu ChihYu,
Eugene Liu H.,
Sheu FeeiYi,
Leu SyJye,
Chiang BorLuen,
Hsiao George,
Lee YuehLun
Publication year - 2010
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1408
Subject(s) - medicine , immunology , ovalbumin , eotaxin , bronchoalveolar lavage , inflammation , chemokine , interleukin 5 , interleukin , cytokine , interleukin 4 , tumor necrosis factor alpha , eosinophil , asthma , lung , immune system
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 allergen‐induced 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 side‐effects 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 hyper‐responsiveness 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‐α‐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. Copyright © 2009 John Wiley & Sons, Ltd.