A new house dust mite–driven and mast cell–activated model of asthma in the guinea pig

Background Animal models are extensively used to study underlying mechanisms in asthma. Guinea pigs share anatomical, pharmacological and physiological features with human airways and may enable the development of a pre‐clinical in vivo model that closely resembles asthma. Objectives To develop an asthma model in guinea pigs using the allergen house dust mite (HDM). Methods Guinea pigs were intranasally sensitized to HDM which was followed by HDM challenges once weekly for five weeks. Antigen‐induced bronchoconstriction (AIB) was evaluated as alterations in Rn (Newtonian resistance), G (tissue damping) and H (tissue elastance) at the first challenge with forced oscillation technique (FOT), and changes in respiratory pattern upon each HDM challenge were assessed as enhanced pause (Penh) using whole‐body plethysmography. Airway responsiveness to methacholine was measured one day after the last challenge by FOT. Inflammatory cells and cytokines were quantified in bronchoalveolar lavage fluid, and HDM‐specific immunoglobulins were measured in serum by ELISA. Airway pathology was evaluated by conventional histology. Results The first HDM challenge after the sensitization generated a marked increase in Rn and G, which was abolished by pharmacological inhibition of histamine, leukotrienes and prostanoids. Repeated weekly challenges of HDM caused increase of Penh and a marked increase in airway hyperresponsiveness for all three lung parameters (Rn, G and H) and eosinophilia. Levels of IgE, IgG1, IgG2 and IL‐13 were elevated in HDM‐treated guinea pigs. HDM exposure induced infiltration of inflammatory cells into the airways with a pronounced increase of mast cells. Subepithelial collagen deposition, airway wall thickness and goblet cell hyperplasia were induced by repeated HDM challenge. Conclusion and Clinical Relevance Repeated intranasal HDM administration induces mast cell activation and hyperplasia together with an asthma‐like pathophysiology in guinea pigs. This model may be suitable for mechanistic investigations of asthma, including evaluation of the role of mast cells.