Marked airway eosinophilia prevents development of airway hyper-responsiveness during an allergic response in IL-5 transgenic mice

Takao Kobayashi, Koji Iijima, Hirohito Kita

Research output: Contribution to journalArticle

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Abstract

Tissue eosinophilia probably plays important roles in the pathophysiology of bronchial asthma and allergic disorders; however, this concept was challenged recently by controversial results in mouse models of bronchial asthma treated with anti-IL-5 Ab and the failure of anti-IL-5 therapy in humans. We have now used a unique model, IL-5 transgenic (TG) mice, to address a fundamental question: is airway eosinophilia beneficial or detrimental in the allergic response? After sensitization and challenge with OVA, IL-5 TG mice showed a marked airway eosinophilia. Surprisingly, these IL-5 TG mice showed lower airway reactivity to methacholine. Immunohistochemical analysis of the lungs revealed a marked peribronchial infiltration of eosinophils, but no eosinophil degranulation. In vitro, mouse eosinophils from peritoneal lavage fluids did not produce superoxide anion, but did produce an anti-inflammatory and fibrotic cytokine, TGF-β1. Indeed, the TGF-β1 levels in bronchoalveolar lavage fluid specimens from IL-5 TG mice directly correlated with airway eosinophilia (r = 0.755). Furthermore, anti-IL-5 treatment of IL-5 TG mice decreased both airway eosinophilia and TGF-β1 levels in bronchoalveolar lavage fluids and increased airway reactivity. Thus, in mice, marked eosinophilia prevents the development of airway hyper-reactivity during an allergic response. Overall, the roles of eosinophils in asthma and in animal models need to be addressed carefully for their potentially detrimental and beneficial effects.

Original languageEnglish (US)
Pages (from-to)5756-5763
Number of pages8
JournalJournal of Immunology
Volume170
Issue number11
StatePublished - Jun 1 2003

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Respiratory Hypersensitivity
Interleukin-5
Eosinophilia
Transgenic Mice
Eosinophils
Asthma
Bronchoalveolar Lavage Fluid
Peritoneal Lavage
Methacholine Chloride
Ascitic Fluid
Superoxides
Anti-Inflammatory Agents
Animal Models

ASJC Scopus subject areas

  • Immunology

Cite this

Marked airway eosinophilia prevents development of airway hyper-responsiveness during an allergic response in IL-5 transgenic mice. / Kobayashi, Takao; Iijima, Koji; Kita, Hirohito.

In: Journal of Immunology, Vol. 170, No. 11, 01.06.2003, p. 5756-5763.

Research output: Contribution to journalArticle

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