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

Clin Exp Allergy. 2005 Aug;35(8):1096-103. doi: 10.1111/j.1365-2222.2005.02299.x.

Abstract

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 microg 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology*
  • Asthma / immunology*
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Eosinophilia / immunology
  • Eosinophils / immunology
  • Esophagitis / immunology*
  • Goblet Cells / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Interleukin-13 / immunology*
  • Lung / immunology
  • Lung / pathology
  • Metaplasia
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Interleukin-13