Superior effect of MP-AzeFlu than azelastine or fluticasone propionate alone on reducing inflammatory markers

Allergy, Asthma & Clinical Immunology

DucTung Nguyen¹  Dennis Castor¹  Mireya Fuentes²  Joaquim Mullol²  Maria Pérez-González²  Jordi Roca-Ferrer²  Isam Alobid²  Sònia Vicens-Artés²  César Picado²  Borja Callejas²  Antonio Valero²  Laura Pujols² 

[1] Clinical Science & Operations, Meda Pharma GmbH & Co. KG (A Mylan Company);Clinical and Experimental Respiratory Immunoallergy, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS);

关键词: Cytokines;    Eosinophil survival;    Nasal mucosa;    Epithelial cells;    MP-AzeFlu;    Azelastine;   

DOI  :  10.1186/s13223-018-0311-4

来源: DOAJ

【 摘 要 】

Abstract Background MP-AzeFlu, intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP), is superior to AZE or FP alone for treatment of allergic rhinitis (AR). However, the precise anti-inflammatory mechanism of action of MP-AzeFlu has not been characterized. Objective To investigate the anti-inflammatory effects of MP-AzeFlu compared with AZE or FP alone in an established in vitro model of eosinophilic inflammation. Methods Nasal mucosal epithelial cells and peripheral blood eosinophils were obtained from human volunteers. Epithelial cells were stimulated with 10% fetal bovine serum (FBS) in the presence of MP-AzeFlu, AZE, or FP (1:102 to 1:105 dilution). Concentrations of interleukin (IL)-6, IL-8, and granulocyte–macrophage colony-stimulating factor (GM-CSF) were measured by ELISA. Eosinophils were incubated in 10% human epithelial cell–conditioned medium (HECM) and survival assessed by trypan blue dye exclusion. Results are expressed as mean ± SEM percentage secretion/survival compared with FBS/HECM (respectively). Results FP and MP-AzeFlu (all dilutions) and AZE (1:102) significantly reduced IL-6 secretion and eosinophil survival compared with positive controls. At 1:102 dilution, IL-6 secretion was significantly lower with MP-AzeFlu (38.3 ± 4.2%, compared with FBS = 100%) than with AZE (76.1 ± 4.9%) or FP (53.0 ± 4.9%). At 1:102 dilution, eosinophil survival was significantly lower with MP-AzeFlu at day 3 (17.5 ± 3.0%) and day 4 (2.4 ± 1.4%, compared with HECM = 100%) than with AZE (day 3: 75.2 ± 7.2%; day 4: 44.0 ± 9.7%) or FP (day 3: 38.5 ± 3.5%; day 4: 14.6 ± 4.0%). Conclusion Greater reductions in cytokine secretion and eosinophil survival observed with MP-AzeFlu in vitro may underlie MP-AzeFlu’s superior clinical efficacy vs. AZE or FP alone observed in AR patients.

【 授权许可】

Unknown