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Clinical & Experimental Allergy

IL-12p40 is essential for the down-regulation of airway hyperresponsiveness in a mouse model of bronchial asthma with prolonged antigen exposure

Authors


Correspondence:
Dr Akihito Yokoyama, Department of Hematology and Respiratory Medicine, Kochi University, Kohasu, Oko-cho, Nankoku-city, Kochi 783-8505, Japan. E-mail: ayokoyama@kochi-u.ac.jp

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.

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