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IL‐12p40 is essential for the down‐regulation of airway hyperresponsiveness in a mouse model of bronchial asthma with prolonged antigen exposure
Author(s) -
Onari Y.,
Yokoyama A.,
Haruta Y.,
Nakashima T.,
Iwamoto H.,
Hattori N.,
Kohno N.
Publication year - 2009
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2008.03131.x
Subject(s) - ovalbumin , eosinophilia , bronchoalveolar lavage , immunology , medicine , asthma , antigen , eosinophil , bronchial hyperresponsiveness , lung , eotaxin , inflammation , pulmonary eosinophilia , respiratory disease
Summary Background We previously reported a mouse model of bronchial asthma showing eosinophilic inflammation, but not airway hyperresponsiveness (AHR), after prolonged antigen exposure. This model showed an increase of IL‐12 in the lung. Objective The aim of this study was to investigate the role of IL‐12p40 in a murine asthma model with prolonged antigen exposures. Methods An ovalbumin (OVA)‐induced asthma model was first established in wild‐type (WT) and IL‐12p40‐deficient (IL‐12p40 −/− ) mice. Both strains of mice were further exposed to either OVA (prolonged exposure group) or phosphate‐buffered saline (positive control group) 3 days per week for 3 weeks. During week 4, both groups of mice were given a final challenge with OVA. Results Prolonged antigen exposures resulted in marked suppression of airway eosinophilia in both WT and IL‐12p40 −/− mice. However, AHR persisted in IL‐12p40 −/− but not in WT mice. There were no significant differences of IL‐5, IL‐13 or IFN‐γ levels in bronchoalveolar lavage fluid between WT and IL‐12p40 −/− mice. The hydroxyproline content of the lung and peribronchial fibrosis were, however, significantly increased in IL‐12p40 −/− mice. Conclusion The results suggest that endogenous IL‐12p40 is essential for inhibition of AHR and peribronchial fibrosis, but not eosinophilic inflammation, in a murine asthma model with prolonged antigen exposures.