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Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma

Gene Therapy volume 13, pages 1414–1421 (2006)Cite this article

Abstract

Interleukin-1 (IL-1) is a proinflammatory cytokine and IL-1 receptor antagonist (IL-1ra) is a natural inhibitor that binds to IL-1 receptor type I without inducing signal transduction. It is suggested that IL-1 is required for allergen-specific T helper type 2 cell activation and the development of airway hyper-responsiveness (AHR), but the immunologic effect of exogenous IL-1ra in allergic asthma remains unclear. To examine the effect of IL-1ra on airway inflammation and immunoeffector cells in allergic asthma, recombinant adenovirus expressing human IL-1ra (Ad-hIL-1ra) was delivered intranasally into ovalbumin (OVA)-immunized mice. Single intranasal administration of Ad-hIL-1ra before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and reduced pulmonary infiltration of eosinophils and neutrophils. Suppression of IL-5 and eotaxin with concomitant enhancement of interferon gamma in bronchoalveolar lavage fluid was also noted in OVA-immunized mice by administration of Ad-hIL-1ra. In addition, histological studies showed that Ad-hIL-1ra was able to decrease OVA-induced peribronchial inflammation. Taken together, our results indicated that administration of Ad-hIL-1ra may have therapeutic potential for the immunomodulatory treatment of allergic asthma.

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Acknowledgements

This work was supported by the grant from National Science Council of Republic of China.

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  1. C-C Wang and C-L Fu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, Republic of China

    C-C Wang, Y-H Yang, Y-C Lo, L-C Wang & B-L Chiang

  2. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

    C-L Fu, Y-H Chuang & B-L Chiang

  3. Department of Pediatrics, Chung-Hsin Municipal Hospital, Taipei, Taiwan, Republic of China

    Y-C Lo

  4. Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China

    D-M Chang

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Correspondence to B-L Chiang.

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Wang, CC., Fu, CL., Yang, YH. et al. Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma. Gene Ther 13, 1414–1421 (2006). https://doi.org/10.1038/sj.gt.3302798

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