Superior effect of MP-AzeFlu than azelastine or fluticasone propionate alone on reducing inflammatory markers
Jordi Roca-Ferrer1,2, Laura Pujols1,2, Maria Pérez-González1,2
11Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
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.
Insights
MP-AzeFlu, a combination nasal spray, significantly reduced inflammatory markers and eosinophil survival more effectively than azelastine hydrochloride (AZE) or fluticasone propionate (FP) alone in an in vitro model. This suggests a mechanism for its superior clinical efficacy in treating allergic rhinitis (AR).
Area of Science:
- Immunology
- Pharmacology
- Rhinology
Background:
- MP-AzeFlu, an intranasal formulation combining azelastine hydrochloride (AZE) and fluticasone propionate (FP), demonstrates superior clinical efficacy in treating allergic rhinitis (AR) compared to AZE or FP monotherapy.
- The precise anti-inflammatory mechanisms underlying the enhanced efficacy of MP-AzeFlu remain incompletely characterized.
Purpose of the Study:
- To investigate and compare the in vitro anti-inflammatory effects of MP-AzeFlu against its individual components, AZE and FP.
- To elucidate the impact of MP-AzeFlu on key inflammatory mediators and cellular responses in an established model of eosinophilic inflammation.
Main Methods:
- Human nasal mucosal epithelial cells and peripheral blood eosinophils were utilized in an in vitro model.
- Epithelial cells were stimulated and treated with MP-AzeFlu, AZE, or FP across a range of dilutions (1:10^2 to 1:10^5).
- Interleukin (IL)-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion was quantified via ELISA, and eosinophil survival was assessed using trypan blue dye exclusion.
Main Results:
- MP-AzeFlu and FP, along with AZE at the highest concentration (1:10^2), significantly reduced IL-6 secretion and eosinophil survival.
- At a 1:10^2 dilution, MP-AzeFlu demonstrated a significantly greater reduction in IL-6 secretion (38.3%) compared to AZE (76.1%) and FP (53.0%).
- MP-AzeFlu also exhibited significantly lower eosinophil survival rates at days 3 (17.5%) and 4 (2.4%) compared to AZE and FP.
Conclusions:
- The superior in vitro reduction in cytokine secretion and eosinophil survival by MP-AzeFlu provides a potential mechanistic explanation for its enhanced clinical effectiveness in allergic rhinitis.
- These findings support the synergistic or additive anti-inflammatory actions of combining azelastine hydrochloride and fluticasone propionate in a single intranasal formulation.
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