Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model

GRANJA?GALEANO, GINA; DAVIO, CARLOS A.; GOLDMAN, ALEJANDRA; ZAPPIA, CARLOS D.; FENOY, IGNACIO; SHAYO, CARINA; MONCZOR, FEDERICO; SOTO, ARIADNA; FERNANDEZ, NATALIA; FITZSIMONS, CARLOS P.

Pharmacology Research & Perspectives

John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Lugar: NY; Año: 2019 vol. 7

2052-1707

Glucocorticoids are among the most effective drugs to treat asthma. However, thesevere adverse effects associated generate the need for its therapeutic optimization.Conversely, though histamine is undoubtedly related to asthma development, thereis a lack of efficacy of antihistamines in controlling its symptoms, which preventstheir clinical application. We have reported that antihistamines potentiate glucocorticoids?responses in vitro and recent observations have indicated that the coadministrationof an antihistamine and a synthetic glucocorticoid has synergistic effectson a murine model of allergic rhinitis. Here, the aim of this work is to establish if thistherapeutic combination could be beneficial in a murine model of asthma. We usedan allergen‐induced model of asthma (employing ovalbumin) to evaluate the effectsof the synthetic glucocorticoid dexamethasone combined with the antihistamineazelastine. Our results indicate that the cotreatment with azelastine and a suboptimaldose of dexamethasone can improve allergic lung inflammation as shown by a decreasein eosinophils in bronchoalveolar lavage, fewer peribronchial and perivascularinfiltrates, and mucin‐producing cells. In addition, serum levels of allergen‐specificIgE and IgG1 were also reduced, as well as the expression of lung inflammatory‐relatedgenes IL‐4, IL‐5, Muc5AC, and Arginase I. The potentiation of dexamethasoneeffects by azelastine could allow to reduce the effective glucocorticoid dose neededto achieve a therapeutic effect. These findings provide first new insights into thepotential benefits of glucocorticoids and antihistamines combination for the treatmentof asthma and grants further research to evaluate this approach in other relatedinflammatory conditions.