title: Effect of fexofenadine on eosinophil-induced changes in epithelial permeability and cytokine release from nasal epithelial cells of patients with seasonal allergic rhinitis.
abstract: Recent studies have suggested that antihistamines, widely used in the treatment of symptoms of patients with allergic rhinitis, may also possess antiinflammatory properties. The mechanisms underlying this property, however, are not clearly understood. We have cultured epithelial cells from nasal biopsy specimens from patients with seasonal allergic rhinitis outside the pollen season and studied the effect of 0 to 10(-3) mol/L fexofenadine, the main active metabolite of terfenadine, on eosinophil-induced changes in electrical resistance (measure of permeability) and release of proinflammatory mediators from these cells. Additionally, we have studied the effect of this drug on eosinophil chemotaxis and adherence to endothelial cells induced by conditioned medium from these human nasal epithelial cell (HNEC) cultures. Incubation of HNEC in the presence of eosinophils treated with opsonized latex beads significantly decreased the electrical resistance of these cultures, an effect that was abrogated by treatment of the cultures with 10(-9) to 10(-3) mol/L fexofenadine. Similarly, incubation of HNEC in the presence of eosinophils treated with latex beads also significantly increased the basal release of the chemokine "regulated upon activation, normal T cell expressed and secreted" (RANTES) (from 96.0 to 613.0 fg/microg cellular protein; p < 0.05), IL-8 (from 42.0 to 198.5 pg/microg cellular protein; p < 0.05), granulocyte-macrophage colony-stimulating factor (GM-CSF) (from 0.54 to 3.4 pg/microg cellular protein; p < 0.05), and soluble intercellular adhesion molecule-1 (sICAM-1) (from 7.8 to 18.4 pg/microg cellular protein; p < 0.05) from HNEC. The eosinophil-induced release of IL-8, GM-CSF, and sICAM-1 from the HNEC was significantly attenuated by treatment with fexofenadine. Analysis of the effects of conditioned medium from HNEC demonstrated that this significantly increased both eosinophil chemotaxis and adherence to endothelial cells. Addition of 10(-6) to 10(-3) mol/L fexofenadine to the conditioned medium significantly attenuated eosinophil chemotaxis and adherence to endothelial cells. These results suggest that fexofenadine may reduce nasal inflammation by modulating the release of proinflammatory mediators and adhesion molecules from HNEC.
authors.affiliation: Academic Department of Respiratory Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, United Kingdom.
authors.forename: M M
authors.initials: MM
authors.lastname: Abdelaziz
authors.forename: J L
authors.initials: JL
authors.lastname: Devalia
authors.forename: O A
authors.initials: OA
authors.lastname: Khair
authors.forename: H
authors.initials: H
authors.lastname: Bayram
authors.forename: A J
authors.initials: AJ
authors.lastname: Prior
authors.forename: R J
authors.initials: RJ
authors.lastname: Davies
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008863:Microspheres; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009895:Opsonin Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D016207:Cytokines; D006633:Histamine Antagonists; D016209:Interleukin-8; D009895:Opsonin Proteins; D011506:Proteins; D018799:Intercellular Adhesion Molecule-1; D016593:Terfenadine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C093230:fexofenadine