Abstract
Introduction: We have developed a guinea pig asthma model that mimics the allergen-induced bronchoconstriction (AIB) and airway hyperresponsiveness (AHR) in humans. This study assessed the influence of treatment with budesonide on AIB, AHR, and levels of IL-5 produced by inflammatory cells.
Method: Guinea pigs were sensitized twice to HDM by aerosol route and then challenged once per week for five consecutive weeks. In one group, HDM-sensitized animals were treated with budesonide before each challenge. Presence of AIB was monitored using plethysmography giving Penh recordings. Changes in the airway resistance induced by methacholine were assessed 24h after the last challenge using the flexiVent™ system. BALF and blood inflammatory cells were assessed for intracellular IL-5 using flow cytometry.
Results: HDM-treated animals showed an increased Penh by more than 200% upon every successive challenge, which was unaffected by budesonide treatment. Lung mechanic measurements documented a marked AHR, expressed as a decrease in PD200, in HDM-treated guinea pigs. This response was not affected by budesonide treatment. The percentage of IL-5-producing CD4 T cells and IL-5 production by granulocytes were significantly increased in HDM-treated animals. Budesonide treatment significantly decreased the HDM-induced IL-5 production in both granulocytes and CD4 T cells.
Conclusions: In this study, downregulation of IL-5 production in inflammatory cells by budesonide treatment does not affect the AIB or AHR. Thus, this novel guinea pig asthma model using HDM as allergen might be a suitable model to study the mechanisms underlying steroid-resistant asthma.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA4081.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019