ORBi: Hacha Jonathan - Nebulized Anti-IL-13 Monoclonal Antibody Fab' Fragment Reduces Allergen-Induced Asthma

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


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/132182

Title :	Nebulized Anti-IL-13 Monoclonal Antibody Fab' Fragment Reduces Allergen-Induced Asthma
Language :	English
Author, co-author :	Hacha, Jonathan [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
	Tomlinson, K []
	Maertens, Ludovic [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Paulissen, Geneviève [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Rocks, Natacha [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
	Foidart, Jean-Michel [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
	Noël, Agnès [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
	Palframan, R []
	Guéders, Maud [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
	Cataldo, Didier [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path. >]
Publication date :	2012
Journal title :	American Journal of Respiratory Cell and Molecular Biology
Publisher :	American Thoracic Society
Volume :	sous presse
Audience :	International
ISSN :	1044-1549
e-ISSN :	1535-4989
City :	New York
Country :	NY
Keywords :	[en] Inflammation ; inhalation ; mouse model ; pulmonary disease ; therapy
Abstract :	[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.
Permalink :	http://hdl.handle.net/2268/132182
DOI :	10.1165/rcmb.2012-0031OC

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