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

Joaquim Mullol,Antonio Valero,Maria Asunción Martínez-Antón,Isam Alobid,Cesar Picado,Eva Méndez-Arancibia,Francisco De Borja Callejas,Jordi Roca-Ferrer,Laura Pujols

doi:10.1186/1465-9921-12-23

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.

Highlights

Antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated
Because mometasone furoate (MF) and DL were diluted in ethanol and dimethyl sulfoxide (DMSO), respectively, and the Human Epithelial Conditioned Media (HECM) added to the eosinophil cultures contained 10% fetal bovine serum (FBS), we investigated the effect of ethanol, DMSO and FBS on eosinophil survival
Effect of FBS on cytokine and soluble intercellular adhesion molecule-1 (sICAM-1) secretion In NM epithelial cell cultures (N = 9), FBS increased the secretion of IL-6, IL-8, GMCSF and soluble intercellular adhesion molecule (sICAM)-1

Summary

Introduction

Antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The increased level of pro-inflammatory mediators plays a role in the eosinophil infiltration of nasal mucosa Some of these cytokines and other mediators such as plateletactivating factor (PAF), adhesion molecules and cysteinyl leukotrienes induce eosinophilopoeisis, cell recruitment from peripheral blood to the site of inflammation, and increase eosinophil survival and activation [7,8,9,10,11,12]. The first line treatment of upper airway inflammation includes corticosteroids and antihistamines [2] Corticosteroids such as mometasone furoate (MF) and others have been shown to be effective in the treatment of allergic rhinitis and rhinosinusitis [13,14]. DL inhibits cytokine secretion from NM and NP epithelial cells, basophils, and mast cells [12,23,24]

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