Abstract
BackgroundMP-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.ObjectiveTo investigate the anti-inflammatory effects of MP-AzeFlu compared with AZE or FP alone in an established in vitro model of eosinophilic inflammation.MethodsNasal 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).ResultsFP 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%).ConclusionGreater 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.
Highlights
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)
After 24 h, the supernatant was harvested from cultures, centrifuged at 400 g for 10 min at room temperature, sterilized through 0.22 μm filters, and stored at -80 °C until used. Because both AZE and FP were diluted in dimethyl sulfoxide (DMSO) when preparing the MP-AzeFlu formulation, we investigated the effect of DMSO at the highest final concentration present in the culture medium on epithelial cell viability and cytokine secretion
Effect of fetal bovine serum (FBS) on cytokine and soluble intercellular adhesion molecule-1 (sICAM)‐1 secretion In nasal mucosal epithelial cell cultures, FBS increased the secretion of IL-6, IL-8, granulocyte–macrophage colony-stimulating factor (GM-CSF), and sICAM-1 compared with control medium (Table 1)
Summary
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). Combined intranasal azelastine hydrochloride (AZE) and intranasal fluticasone propionate (FP) in a single intranasal formulation (MP-AzeFlu) is recommended as more effective than monotherapy [8] and as a firstline option for moderate-to-severe AR [7, 8]. A retrospective US claim database study of AR patients with comorbid asthma has shown, that the AR and asthma related therapy costs were lower when the patients have been treated with MP-AzeFlu than with a free combination of intranasal steroid and intranasal antihistamine [18]
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