AZELASTINE POTENTIATES ANTI-ASTHMATIC DEXAMETHASONE EFFECT ON A MURINE ASTHMA MODEL

A SOTO; GRANJA GALEANO; FENOY I; DAVIO CA; FERNANDEZ, N; SHAYO, C; FITZSIMONS CP; GOLDMAN A; MONCZOR, F

Pharmacology Research & Perspectives

Wiley

Año: 2019

AbstractBackground and Purpose: While glucocorticoids are the most effective therapy to treat asthma, the existence of important adverse effects reflects the need of new therapeutic strategies. On the other hand, even though histamine is undoubtedly related to the development of asthma, antihistamines have demonstrated to be ineffective in controlling the disease symptoms. Considering that we have previously reported that antihistamines potentiate glucocorticoid response in-vitro, the aim of this work was to establish if this could be of clinical relevance for the treatment of asthma.Experimental Approach: We used a well-known allergen-induced murine model of asthma to study the effectiveness of the co-treatment with a corticoid, dexamethasone, and an anti-allergic drug, the antihistamine azelastine.Key Results: We observed that treatment with azelastine and a suboptimal dose of dexamethasone can improve allergic lung inflammation as shown by the decrease in eosinophils in bronchoalveolar lavage (BAL), fewer peribronchial and perivascular infiltrate and mucin-producing cells. In addition, a diminished level of allergen specific IgE and IgG1 was detected, as well as a reduction in lung expression of inflammation-related genes IL-4, IL-5, Muc5ac and Arginase I.Conclusion and Implications: Our results showed that azelastine potentiates the anti-inflammatory dexamethasone effect, allowing a reduction of the effective glucocorticoid concentration needed to achieve a therapeutic effect. These findings provide new insights into the benefits of a combined therapy for the relief of asthma symptoms and grants further research to evaluate this approach for the treatment of inflammatory related conditions