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Nebulized anti-IL-13 monoclonal antibody Fab' fragment reduces allergen-induced asthma
- Source :
- American journal of respiratory cell and molecular biology. 47(5)
- Publication Year :
- 2012
-
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.
- Subjects :
- Pulmonary and Respiratory Medicine
Male
medicine.drug_class
Ovalbumin
Clinical Biochemistry
Immunoglobulin E
medicine.disease_cause
Monoclonal antibody
Bronchoconstrictor Agents
Antibodies, Monoclonal, Murine-Derived
Immunoglobulin Fab Fragments
Mice
Allergen
Administration, Inhalation
medicine
Animals
Anti-Asthmatic Agents
Molecular Biology
Lung
Methacholine Chloride
Mice, Inbred BALB C
Interleukin-13
biology
business.industry
Airway Resistance
Nebulizers and Vaporizers
Cell Biology
respiratory system
Eosinophil
Allergens
medicine.disease
Asthma
respiratory tract diseases
medicine.anatomical_structure
Matrix Metalloproteinase 9
Bronchial hyperresponsiveness
Monoclonal
Immunology
biology.protein
Airway Remodeling
Matrix Metalloproteinase 2
Antibody
Inflammation Mediators
business
STAT6 Transcription Factor
Bronchoalveolar Lavage Fluid
Subjects
Details
- ISSN :
- 15354989
- Volume :
- 47
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- American journal of respiratory cell and molecular biology
- Accession number :
- edsair.doi.dedup.....921848ad8da88fc496dfbdfb46887845