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Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model

Glucocorticoids are among the most effective drugs to treat asthma. However, the severe adverse effects associated generate the need for its therapeutic optimization. Conversely, though histamine is undoubtedly related to asthma development, there is a lack of efficacy of antihistamines in controlli...

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Autores principales: Zappia, Carlos D., Soto, Ariadna, Granja‐Galeano, Gina, Fenoy, Ignacio, Fernandez, Natalia, Davio, Carlos A., Shayo, Carina, Fitzsimons, Carlos P., Goldman, Alejandra, Monczor, Federico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818730/
https://www.ncbi.nlm.nih.gov/pubmed/31687162
http://dx.doi.org/10.1002/prp2.531
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author Zappia, Carlos D.
Soto, Ariadna
Granja‐Galeano, Gina
Fenoy, Ignacio
Fernandez, Natalia
Davio, Carlos A.
Shayo, Carina
Fitzsimons, Carlos P.
Goldman, Alejandra
Monczor, Federico
author_facet Zappia, Carlos D.
Soto, Ariadna
Granja‐Galeano, Gina
Fenoy, Ignacio
Fernandez, Natalia
Davio, Carlos A.
Shayo, Carina
Fitzsimons, Carlos P.
Goldman, Alejandra
Monczor, Federico
author_sort Zappia, Carlos D.
collection PubMed
description Glucocorticoids are among the most effective drugs to treat asthma. However, the severe adverse effects associated generate the need for its therapeutic optimization. Conversely, though histamine is undoubtedly related to asthma development, there is a lack of efficacy of antihistamines in controlling its symptoms, which prevents their clinical application. We have reported that antihistamines potentiate glucocorticoids’ responses in vitro and recent observations have indicated that the coadministration of an antihistamine and a synthetic glucocorticoid has synergistic effects on a murine model of allergic rhinitis. Here, the aim of this work is to establish if this therapeutic combination could be beneficial in a murine model of asthma. We used an allergen‐induced model of asthma (employing ovalbumin) to evaluate the effects of the synthetic glucocorticoid dexamethasone combined with the antihistamine azelastine. Our results indicate that the cotreatment with azelastine and a suboptimal dose of dexamethasone can improve allergic lung inflammation as shown by a decrease in eosinophils in bronchoalveolar lavage, fewer peribronchial and perivascular infiltrates, and mucin‐producing cells. In addition, serum levels of allergen‐specific IgE and IgG1 were also reduced, as well as the expression of lung inflammatory‐related genes IL‐4, IL‐5, Muc5AC, and Arginase I. The potentiation of dexamethasone effects by azelastine could allow to reduce the effective glucocorticoid dose needed to achieve a therapeutic effect. These findings provide first new insights into the potential benefits of glucocorticoids and antihistamines combination for the treatment of asthma and grants further research to evaluate this approach in other related inflammatory conditions.
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spelling pubmed-68187302019-11-04 Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model Zappia, Carlos D. Soto, Ariadna Granja‐Galeano, Gina Fenoy, Ignacio Fernandez, Natalia Davio, Carlos A. Shayo, Carina Fitzsimons, Carlos P. Goldman, Alejandra Monczor, Federico Pharmacol Res Perspect Original Articles Glucocorticoids are among the most effective drugs to treat asthma. However, the severe adverse effects associated generate the need for its therapeutic optimization. Conversely, though histamine is undoubtedly related to asthma development, there is a lack of efficacy of antihistamines in controlling its symptoms, which prevents their clinical application. We have reported that antihistamines potentiate glucocorticoids’ responses in vitro and recent observations have indicated that the coadministration of an antihistamine and a synthetic glucocorticoid has synergistic effects on a murine model of allergic rhinitis. Here, the aim of this work is to establish if this therapeutic combination could be beneficial in a murine model of asthma. We used an allergen‐induced model of asthma (employing ovalbumin) to evaluate the effects of the synthetic glucocorticoid dexamethasone combined with the antihistamine azelastine. Our results indicate that the cotreatment with azelastine and a suboptimal dose of dexamethasone can improve allergic lung inflammation as shown by a decrease in eosinophils in bronchoalveolar lavage, fewer peribronchial and perivascular infiltrates, and mucin‐producing cells. In addition, serum levels of allergen‐specific IgE and IgG1 were also reduced, as well as the expression of lung inflammatory‐related genes IL‐4, IL‐5, Muc5AC, and Arginase I. The potentiation of dexamethasone effects by azelastine could allow to reduce the effective glucocorticoid dose needed to achieve a therapeutic effect. These findings provide first new insights into the potential benefits of glucocorticoids and antihistamines combination for the treatment of asthma and grants further research to evaluate this approach in other related inflammatory conditions. John Wiley and Sons Inc. 2019-10-29 /pmc/articles/PMC6818730/ /pubmed/31687162 http://dx.doi.org/10.1002/prp2.531 Text en © 2019 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Zappia, Carlos D.
Soto, Ariadna
Granja‐Galeano, Gina
Fenoy, Ignacio
Fernandez, Natalia
Davio, Carlos A.
Shayo, Carina
Fitzsimons, Carlos P.
Goldman, Alejandra
Monczor, Federico
Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
title Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
title_full Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
title_fullStr Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
title_full_unstemmed Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
title_short Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
title_sort azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818730/
https://www.ncbi.nlm.nih.gov/pubmed/31687162
http://dx.doi.org/10.1002/prp2.531
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