Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma

J Allergy Clin Immunol. 2007 Dec;120(6):1324-31. doi: 10.1016/j.jaci.2007.07.051. Epub 2007 Sep 24.


Background: IL-25 (IL-17E), a member of the IL-17 family of immunoregulatory cytokines, has been implicated in the regulation of type 2 immunity. Its roles in antigen-driven airway inflammation and airway hyperresponsiveness (AHR) remain to be fully established.

Objective: We sought to determine whether a neutralizing antibody against IL-25 represents a novel therapeutic for airway inflammation and hyperresponsiveness.

Methods: We generated a neutralizing mAb against IL-25 and used this to inhibit IL-25 in a mouse model of allergic airway disease.

Results: Blocking IL-25 in an experimental model of allergic asthma prevented AHR, a critical feature of clinical asthma. Administration of anti-IL-25 mAb during the sensitization phase resulted in significantly reduced levels of IL-5 and IL-13 production, eosinophil infiltration, goblet cell hyperplasia, and serum IgE secretion, and prevented AHR. Even more striking was the ability of anti-IL-25 mAb, administered only during the challenge phase of the response, specifically to prevent AHR even during an ongoing type 2 inflammatory response in the lungs.

Conclusion: IL-25 is critical for development of AHR.

Clinical implications: We define a novel pathway for the induction of AHR and suggest that IL-25 represents an important therapeutic target for the treatment of asthma. Significantly, our antibody also blocks the binding of human IL-25 to its receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use
  • Asthma / immunology*
  • Asthma / physiopathology
  • Asthma / therapy*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / prevention & control*
  • Disease Models, Animal
  • Female
  • Interleukin-13 / metabolism
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / immunology
  • Interleukin-17 / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / immunology


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • IL25 protein, human
  • Interleukin-13
  • Interleukin-17