Abstract
Azelastine was suggested as a supplementary choice of glucocorticoid for the control of moderate to severe allergic rhinitis (AR). However, the underlying mechanism has not been completely understood. In this study, primary cultured nasal epithelial cells and bronchial epithelial cells were stimulated with proinflammatory cytokines (IL-1β and IL-17A) and anti-inflammatory agents (azelastine and budesonide) in vitro. The expression of intercellular adhesion molecule 1 (ICAM-1) and mitogen-activated protein kinase phosphatase-1 (MKP-1) was examined using qPCR and ELISA, respectively. Moreover, the additive effects of azelastine and budesonide nasal spray on nasal ICAM-1 level and total nasal symptom scores were evaluated in six uncontrolled severe AR patients by budesonide nasal spray alone. We found azelastine significantly inhibited cytokine-induced ICAM-1 upregulation, which is reversed by MKP-1 silencing. Azelastine and budesonide additively increased MKP-1 expression and inhibited ICAM-1 expression in vitro. After treatment for two consecutive weeks, combined azelastine and budesonide nasal spray significantly decreased nasal ICAM-1 level and TNSS in six uncontrolled AR patients. Our findings suggested that azelastine is able to additively enhance the anti-inflammatory effect of budesonide by modulating MKP-1 expression, which may implicate in the treatment of uncontrolled severe AR.
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Acknowledgments
This study was supported by the National Natural Science Fund of China (No. 81260156, 81271054, 81371071) and grants from the Ministry of Hygiene (No. 201202005, 2014BAI07B04).
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X. Luo and R. Ma have contributed equally to this study.
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Luo, X., Ma, R., Wu, X. et al. Azelastine enhances the clinical efficacy of glucocorticoid by modulating MKP-1 expression in allergic rhinitis. Eur Arch Otorhinolaryngol 272, 1165–1173 (2015). https://doi.org/10.1007/s00405-014-3191-3
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DOI: https://doi.org/10.1007/s00405-014-3191-3