Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354)

Authors

  • C. Blanchard,

    1. Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • A. Mishra,

    1. Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • H. Saito-Akei,

    1. Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • P. Monk,

    1. Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge, UK
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  • I. Anderson,

    1. Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge, UK
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  • M. E. Rothenberg

    1. Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Dr Marc E. Rothenberg, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
E-mail: Rothenberg@cchmc.org

Summary

Background Allergic asthma is a complex disorder characterized by local and systemic T helper type 2 -cell responses such as the production of IL-13, a cytokine associated with the induction of airway hyper-responsiveness (AHR), chronic pulmonary eosinophilia, airway mucus overproduction and eosinophilic oesophagitis.

Objective Our study aimed to address the therapeutic potential of a human anti-human IL-13 IgG4 monoclonal antibody (CAT-354) in a murine model of respiratory and oesophageal inflammation induced by intratracheal human IL-13.

Methods BALB/c mice were treated on days 1 and 3 with CAT-354 (intraperitoneal injection), and human IL-13 was injected intratracheally on days 2 and 4. AHR to methacholine, airway eosinophilia in bronchoalveolar lavage fluid, histologic analysis of goblet cell metaplasia and oesophageal eosinophilia were evaluated.

Results Human IL-13 induced airway eosinophilia and goblet cell metaplasia in mice in a dose-dependent manner. Moreover, intratracheal dosing with 25 μg of human IL-13 was sufficient to induce AHR, goblet cell metaplasia and oesophageal eosinophilia. Pretreatment with CAT-354 significantly reduced AHR, airway eosinophilia and oesophageal eosinophilia.

Conclusion These results demonstrate that anti-human IL-13 (CAT-354) is a potential therapeutic treatment for allergic airway and oesophageal diseases.

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