1. Nebulized anti-IL-13 monoclonal antibody Fab' fragment reduces allergen-induced asthma.
- Author
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Hacha J, Tomlinson K, Maertens L, Paulissen G, Rocks N, Foidart JM, Noel A, Palframan R, Gueders M, and Cataldo DD
- Subjects
- Administration, Inhalation, Airway Remodeling drug effects, Airway Resistance drug effects, Allergens immunology, Animals, Asthma immunology, Bronchoalveolar Lavage Fluid, Bronchoconstrictor Agents pharmacology, Inflammation Mediators metabolism, Interleukin-13 immunology, Lung drug effects, Lung pathology, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Methacholine Chloride pharmacology, Mice, Mice, Inbred BALB C, Nebulizers and Vaporizers, Ovalbumin immunology, STAT6 Transcription Factor metabolism, Anti-Asthmatic Agents administration & dosage, Antibodies, Monoclonal, Murine-Derived administration & dosage, Asthma drug therapy, Immunoglobulin Fab Fragments administration & dosage
- Abstract
IL-13 is a prototypic T helper type 2 cytokine and a central mediator of the complex cascade of events leading to asthmatic phenotype. Indeed, IL-13 plays key roles in IgE synthesis, bronchial hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis, and eosinophil infiltration. We assessed the potential efficacy of inhaled anti-IL-13 monoclonal antibody Fab' fragment on allergen-induced airway inflammation, hyperresponsiveness, and remodeling in an experimental model of allergic asthma. Anti-IL-13 Fab' was administered to mice as a liquid aerosol generated by inExpose inhalation system in a tower allowing a nose-only exposure. BALB/c mice were treated by PBS, anti-IL-13 Fab', or A33 Fab' fragment and subjected to ovalbumin exposure for 1 and 5 weeks (short-term and long-term protocols). Our data demonstrate a significant antiasthma effect after nebulization of anti-IL-13 Fab' in a model of asthma driven by allergen exposure as compared with saline and nonimmune Fab fragments. In short- and long-term protocols, administration of the anti-IL-13 Fab' by inhalation significantly decreased bronchial responsiveness to methacholine, bronchoalveolar lavage fluid eosinophilia, inflammatory cell infiltration in lung tissue, and many features of airway remodeling. Levels of proinflammatory mediators and matrix metalloprotease were significantly lower in lung parenchyma of mice treated with anti-IL-13 Fab'. These data demonstrate that an inhaled anti-IL-13 Fab' significantly reduces airway inflammation, hyperresponsiveness, and remodeling. Specific neutralization of IL-13 in the lungs using an inhaled anti-IL-13 Fab' could represent a novel and effective therapy for the treatment of asthma.
- Published
- 2012
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