Mometasone and desloratadine additive effect on eosinophil survival and cytokine secretion from epithelial cells

Abstract

BackgroundAlthough antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps.MethodsEpithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10-11M-10-5M) with/without desloratadine (10-5M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10-11M-10-5M) and/or desloratadine (10-5M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control.ResultsFetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10-5M desloratadine and 10-9M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10-11M) and desloratadine (10-5M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone.ConclusionsThese results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone.

Fluticasone Furoate Inhibits Cytokine Secretion from Nasal Epithelial Cells and Reduces Eosinophil Survival in an in vitro Model of Eosinophilic Inflammation

“…Since previous studies have shown that nonstimulated epithelial cells produce low levels of cytokines [14,21,22,23,24,25,26], human epithelial cell-conditioned media (HECM) was generated by incubating cells with FBS at 10% for 24 h. The culture supernatant (HECM) was harvested from wells, centrifuged at 400 g (10 min, 25°C), sterilized through 0.22-μm filters and stored at -80°C until used. To study the effect of FF, cells were incubated with 10% FBS in the presence or absence of different concentrations of FF (from 10 -12 to 10 -7 M ) for 6-24 h. In order to avoid attributing the different effects of FBS to differentiation in batches and sources, the same manufacturing batch was used in all experiments.…”

“…Epithelial cells from nasal mucosa were isolated by protease digestion using a technique reported previously [13,14,15,21,22,23,24,25,26]. Viability of cells was assessed by trypan blue-dye exclusion using a hemocytometer.…”

“…Using this model, we have reported that a number of systemic (dexamethasone), topical (beclometasone dipropionate, fluticasone propionate, triamcinolone acetonide, budesonide and mometasone furoate) GC, and to a lesser extent antihistamines (desloratadine) and antileukotrienes (montelukast), inhibit the release of cytokines and adhesion molecules from NM epithelial cell cultures [22,23,24,25,26]. In addition, we have reported that these drugs also inhibit eosinophil survival induced by NM epithelial cell secretions [13,15,21,22,23,24,25]. …”

“…To study the mechanisms involved in the etiology of upper airway inflammatory diseases and the mechanism of action of anti-inflammatory drugs, an in vitro model of interaction between cultured primary isolated NM epithelial cells and isolated peripheral blood eosinophils has been developed [13,15,21,22,23,24,25]. Using this model, we have reported that a number of systemic (dexamethasone), topical (beclometasone dipropionate, fluticasone propionate, triamcinolone acetonide, budesonide and mometasone furoate) GC, and to a lesser extent antihistamines (desloratadine) and antileukotrienes (montelukast), inhibit the release of cytokines and adhesion molecules from NM epithelial cell cultures [22,23,24,25,26].…”

Treatment Evaluation with Mometasone Furoate, Alone or in Combination with Desloratadine/ Montelukast in Moderate Severe Allergic Rhinitis

“…A recent study [8] has demonstrated in vitro anti-infl ammatory eff ect greater on eosinophilic infl ammation using the combination of mometasone furoate and desloratadine. Another study made by Navarro [9] shows that most physicians prefer the combination between oral antihistamine and intranasal corticosteroids regardless of the rhinitis frequency and intensity.…”