Nebulized Anti-IL-13 Monoclonal Antibody Fab' Fragment Reduces Allergen-Induced Asthma

[en] Rationale: Interleukin-13 (IL-13) is a prototypic Th2 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. Objectives: 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. Methods: BALB/c mice were treated by PBS, anti-IL-13 Fab' or A33 Fab' fragment and subjected to ovalbumin (OVA) exposure for 1 and 5 weeks (short term (ST) and long term (LT) protocols). Measurements and Main Results: Our data demonstrate a significant anti-asthma effect following nebulization of anti-IL-13 Fab' in a model of asthma driven by allergen exposure as compared to saline and non-immune Fab fragments. In short and long terms protocols, administration of the anti-IL-13 Fab' by inhalation significantly decreased bronchial responsiveness to methacholine, BALF eosinophilia, inflammatory cell infiltration in lung tissue, and many features of airway remodeling. Levels of pro-inflammatory mediators and matrix metalloprotease levels were significantly lower in lung parenchyma of mice treated with anti-IL-13 Fab'. Conclusions: 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Hacha, Jonathan ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.

Tomlinson, K

Maertens, Ludovic ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Paulissen, Geneviève ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Rocks, Natacha ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique

Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Palframan, R

Guéders, Maud ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.

Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.

Language :

English

Title :

Nebulized Anti-IL-13 Monoclonal Antibody Fab' Fragment Reduces Allergen-Induced Asthma

Publication date :

2012

Journal title :

American Journal of Respiratory Cell and Molecular Biology

ISSN :

1044-1549

eISSN :

1535-4989

Publisher :

American Thoracic Society, New York, United States - New York

Volume :

sous presse

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 13 October 2012

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