Nebulized anti-IL-13 monoclonal antibody Fab' fragment reduces allergen-induced asthma.
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.
Laboratory of Tumors and Developmental Biology and Department of Respiratory Diseases, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA)-Research (GIGA-I³ and GIGA-Cancer), University of Liege and Centre Hospitalier Universitaire, Liege (Sart-Tilman), Belgium.
Jonathan
J
Hacha
Kate
K
Tomlinson
Ludovic
L
Maertens
Geneviève
G
Paulissen
Natacha
N
Rocks
Jean-Michel
JM
Foidart
Agnès
A
Noel
Roger
R
Palframan
Maud
M
Gueders
Didier D
DD
Cataldo
D000280:Administration, Inhalation; D056151:Airway Remodeling / Q000187:drug effects; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000276:immunology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009330:Nebulizers and Vaporizers; D010047:Ovalbumin / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000378:metabolism
D000485:Allergens; D018927:Anti-Asthmatic Agents; D058846:Antibodies, Monoclonal, Murine-Derived; D016085:Bronchoconstrictor Agents; D007140:Immunoglobulin Fab Fragments; D018836:Inflammation Mediators; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D016210:Methacholine Chloride; D010047:Ovalbumin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse