Murine model of steroid-resistant neutrophilic bronchial asthma as an attempt to simulate human pathology

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, whic...

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Bibliographic Details
Published in:Journal of immunological methods 2022-06, Vol.505, p.113268-113268, Article 113268
Main Authors: Shilovskiy Igor, P., Nikolskii Aleksandr, A., Kovchina Valeriya, I., Vishniakova Lyudmila, I., Yumashev Kirill, V., Barvinskaia Ekaterina, D., Kaganova Mariya, M., Korneev Artem, V., Turenko Vladislav, N., Brylina Vera, E., Petukhova Olga, A., Kudlay Dmitry, A., Khaitov Musa, R.
Format: Article
Language:English
Subjects:
Bronchial asthma
Murine model
Neutrophilic inflammation
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Summary:Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, which is associated with neutrophilic inflammation and resistant to conventional corticosteroid therapy. Contrary to eosinophil-predominant airway inflammation neutrophilic BA is developed through Th1- and Th17-immune responses. However, the etiology of corticoid insensitive neutrophilic BA is still remains unclear. Therefore, in the current study we developed a mouse model of BA with predominant neutrophilic rather than eosinophilic pulmonary inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund's adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed the main BA manifestations: production of allergen specific IgE, development of airway hyperreactivity, airway remodeling and pulmonary neutrophilic inflammation. Moreover, this pathology developed through Th1- and Th17-dependent mechanisms and mice with induced neutrophilic BA phenotype responded poorly to dexamethasone treatment, that coincide to clinical observations. The established mouse model could be useful both for studying the pathogenesis and for testing novel approaches to control neutrophilic BA.
ISSN:0022-1759
1872-7905
DOI:10.1016/j.jim.2022.113268