Desloratadine inhibits GM-CSF secretion from nasal mucosa and polyps and eosinophil survival induced by epithelial cells

Abstract

Rationale Epithelial cells release cytokines such as GM-CSF that contribute to eosinophil inflammation in allergic rhinitis and nasal polyposis. The aim of this study was to investigate the effect of desloratadine on both GM-CSF secretion and eosinophil survival. Methods Epithelial cells from nasal mucosa (NM) and polyps (NP) were cultured and stimulated with 10% fetal bovine serum (FBS) with added desloratadine for 24 hr. GM-CSF was measured in culture supernatants (ECM) by ELISA. Peripheral blood eosinophils were cultured with ECM and desloratadine and eosinophil survival assessed by Trypan blue dye exclusion. Results are expressed as mean ± SEM of GM-CSF secretion (pg/ml) or eosinophil survival (%). Results FBS increased GM-CSF secretion (p<0.01) in epithelial cell cultures from both NM (414 ± 106, n=9) and NP (256 ± 142, n=9), compared to control media (NM=9 ± 3; NP=20 ± 11). GM-CSF-induced secretion was significantly inhibited (p<0.05) by desloratadine in both NM (up to −77%) and NP (up to −69%). Desloratadine also showed an inhibitory effect on eosinophil survival induced by ECM from both NM and NP. At 72 hr, 10-5 M desloratadine inhibited (p<0.05) eosinophil survival induced by ECM from NM (15 ± 8%, n=6) and NP (12 ± 8%, n=8) compared to ECM alone (NM=33 ± 9%; NP=43 ± 10%). Conclusions Desloratadine inhibits both GM-CSF secretion from both nasal mucosa and nasal polyp epithelial cells and eosinophil survival induced by epithelial cell secretions, suggesting that this H1 antagonist may have an antiinflammatory effect on eosinophil inflammation.