Efficacy of inhaled anti-IL-13 mAb in a mouse model of asthma

Interleukin-13 (IL-13) is a prototypic Th2 cytokine and a potential cornerstone of asthma pathology. IL-13 is involved in IgE synthesis, bronchial hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis and eosinophil infiltration. We assessed the potential efficacy of an inhaled high affinity monoclonal antibody (mAb) Fab' fragment neutralizing IL-13 against allergen-induced inflammation and hyperresponsiveness. BALB/c mice were subjected to ovalbumin (OVA) exposure for 1, 5, and 10 weeks referred to as short term (ST), intermediate term (IT) and long term (LT) protocols respectively. The antibody was administered as an aerosol generated by inExpose® in a tower allowing a nose-only exposure. In a one-week OVA-exposure model (ST), we assessed the effectiveness of different doses of anti-IL-13 (0.5 to 5 mg/ml). We report a dose-dependent increase of the anti-inflammatory effect reaching a maximum at a 5 mg/ml. Airway responsiveness to methacholine was measured by using the flexiVent® system. In the different protocols used in this study, administration of the anti-IL-13 Fab' by inhalation significantly decreased bronchial responsiveness to methacholine, BALF eosinophilia, inflammatory cell infiltration in lung tissue, mucus cell upregulation, peribronchial collagen deposition and smooth muscle hyperplasia. After 1 and 5 weeks of allergen exposure (ST and IT), levels of pro-inflammatory mediators IL-13, IL-4, IL-5, CCL-11, MMP-2 and MMP-9 were significantly lower in lung parenchyma when mice were treated by the IL-13 neutralizing antibody. In conclusion, our data generated in a rodent model suggest that inhaled anti-IL-13 Fab' could represent a novel and effective therapy for the treatment of asthma.