Inhibition of human interleukin‐13‐induced respiratory and oesophageal inflammation by anti‐human‐interleukin‐13 antibody (CAT‐354)

Abstract

Summary: Background Allergic asthma is a complex disorder characterized by local and systemic T helper type 2 ‐cell responses such as the production of IL‐13, a cytokine associated with the induction of airway hyper‐responsiveness (AHR), chronic pulmonary eosinophilia, airway mucus overproduction and eosinophilic oesophagitis. Objective Our study aimed to address the therapeutic potential of a human anti‐human IL‐13 IgG4 monoclonal antibody (CAT‐354) in a murine model of respiratory and oesophageal inflammation induced by intratracheal human IL‐13. Methods BALB/c mice were treated on days 1 and 3 with CAT‐354 (intraperitoneal injection), and human IL‐13 was injected intratracheally on days 2 and 4. AHR to methacholine, airway eosinophilia in bronchoalveolar lavage fluid, histologic analysis of goblet cell metaplasia and oesophageal eosinophilia were evaluated. Results Human IL‐13 induced airway eosinophilia and goblet cell metaplasia in mice in a dose‐dependent manner. Moreover, intratracheal dosing with 25 μg of human IL‐13 was sufficient to induce AHR, goblet cell metaplasia and oesophageal eosinophilia. Pretreatment with CAT‐354 significantly reduced AHR, airway eosinophilia and oesophageal eosinophilia. Conclusion These results demonstrate that anti‐human IL‐13 (CAT‐354) is a potential therapeutic treatment for allergic airway and oesophageal diseases.