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A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

Gene Therapy volume 10, pages 2119–2125 (2003)Cite this article

Abstract

Interleukin 4 (IL-4) is essential for the switching of B cells to IgE antibody production and for the maturation of T helper (Th) cells toward the Th2 phenotype. These mechanisms are thought to play a crucial role in the pathogenesis of the allergic airway inflammation observed in asthma. In the present study, we examined the anti-inflammatory effects of DNA administration of murine IL-4 mutant Q116D/Y119D (IL-4 double mutant, IL-4DM), which binds to the IL-4 receptor α and is an antagonist for IL-4. Immunization of BALB/c mice with alum-adsorbed ovalbumin (OVA) followed by aspiration with aerosolized OVA resulted in the development of allergic airway inflammation. A single administration of IL-4DM DNA before the aerosolized OVA challenge protected the mice from the subsequent induction of allergic airway inflammation. Serum IgE level and extent of eosinophil infiltration in bronchoalveolar lavage (BAL) from IL-4DM DNA-administered mice were significantly lower than those in BAL from control plasmid-immunized mice. In our study, IL-4 or IL-4 mutants were not detected in sera from mice that had received a single administration of IL-4DM DNA. The results of this study provide evidence for the potential utility of IL-4 mutant antagonist DNA inoculation as an approach to gene therapy for asthma.

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Acknowledgements

This work was supported by Health Science Research Grants from the Ministry of Health, Labor and Welfare of Japan and the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Mie University School of Medicine, Mie, Japan

    K Nishikubo, S Tamaki, N Yuda, M Kai & Y Adachi

  2. Kyurin Omtest Laboratory Department, Kyurin Co., Fukuoka, Japan

    Y Murata

  3. Primmune KK, Osaka, Japan

    K Sugama

  4. Department of Pathology, Mie University School of Medicine, Mie, Japan

    K Imanaka-Yoshida

  5. Department of Bioregulation, Mie University School of Medicine, Mie, Japan

    S Takamura & Y Yasutomi

  6. Biozentrum, Phygologiscehe Chemie II, Universitat Wurzburg, Wurzburg, Germany

    W Sebald

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Nishikubo, K., Murata, Y., Tamaki, S. et al. A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma. Gene Ther 10, 2119–2125 (2003). https://doi.org/10.1038/sj.gt.3302131

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  • DOI: https://doi.org/10.1038/sj.gt.3302131

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