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
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

@article{f97cde6f288b436aabdb7676ba1d167d,
title = "Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice",
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.",
keywords = "Adenoviral vector, Airway inflammation, Asthma, Interleukin-10, Interleukin-12",
author = "Hsu, {Chih Yu} and {Eugene Liu}, H. and Sheu, {Feei Yi} and Leu, {Sy Jye} and Chiang, {Bor Luen} and George Hsiao and Lee, {Yueh Lun}",
year = "2010",
month = "1",
doi = "10.1002/jgm.1408",
language = "English",
volume = "12",
pages = "11--21",
journal = "Journal of Gene Medicine",
issn = "1099-498X",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - Synergistic therapeutic effects of combined adenovirus-mediated interleukin-10 and interleukin-12 gene therapy on airway inflammation in asthmatic mice

AU - Hsu, Chih Yu

AU - Eugene Liu, H.

AU - Sheu, Feei Yi

AU - Leu, Sy Jye

AU - Chiang, Bor Luen

AU - Hsiao, George

AU - Lee, Yueh Lun

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

KW - Adenoviral vector

KW - Airway inflammation

KW - Asthma

KW - Interleukin-10

KW - Interleukin-12

UR - http://www.scopus.com/inward/record.url?scp=75449085690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75449085690&partnerID=8YFLogxK

U2 - 10.1002/jgm.1408

DO - 10.1002/jgm.1408

M3 - Article

VL - 12

SP - 11

EP - 21

JO - Journal of Gene Medicine

JF - Journal of Gene Medicine

SN - 1099-498X

IS - 1

ER -