Therapeutic efficacy of an anti-IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma

Felix R. Shardonofsky, Joe Venzor, Roberto Barrios, Khai Pang Leong, David P. Huston

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Background: IL-5 is central to the pathogenesis of airway eosinophilic inflammation and hyperresponsiveness associated with both atopic and nonatopic asthma. The therapeutic potential of IL-5 antagonists in asthma is supported by the inhibition of airway eosinophilia and hyperresponsiveness in animal models receiving neutralizing anti-IL-5 mAbs intravenously or intraperitoneally. Objective: The purpose of this study was to test the hypothesis that mAbs against IL-5 delivered by way of the respiratory tract are as effective as those delivered intraperitoneally in diminishing the pulmonary eosinophilic inflammation and airway hyperresponsiveness in a murine model of ovalbumin-induced asthma. Methods: Ovalbumin-sensitized Balb/c mice were given an anti-IL-5 mAb delivered intranasally or an isotype- matched control mAb delivered intranasally before respiratory challenge with ovalbumin. Outcome variables included respiratory system resistance responses to methacholine, bronchoalveolar lavage fluid cellularity, and lung histopathology. Results: Anti-IL-5 mAbs administered intranasally to ovalbumin-sensitized and challenged mice significantly decreased eosinophil counts in bronchoalveolar lavage fluid and lung tissue and significantly reduced airway hyperresponsiveness relative to ovalbumin-sensitized and challenged mice that received either no mAb treatment or an isotype-matched control mAb. Similar results were obtained when an anti-IL-5 mAb was given intraperitoneally. Conclusion: This is the first study to demonstrate that delivery of anti-IL-5 mAbs into the respiratory tract is efficacious in attenuating the asthma phenotype in a murine model. These results provide impetus for the development of inhaled IL-5 antagonists for the treatment of human asthma.

Original languageEnglish (US)
Pages (from-to)215-221
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume104
Issue number1
DOIs
StatePublished - 1999

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • Eosinophils
  • IL-5
  • Inhaled therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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