EFFECT OF FEXOFENADINE ON EOSINOPHIL-INDUCED CHANGES IN EPITHELIAL PERMEABILITY AND CYTOKINE RELEASE FROM NASAL EPITHELIAL-CELLS OF PATIENTS WITH SEASONAL ALLERGIC RHINITIS

Recent studies have suggested that antihistamines, widely used in the treatment of symptoms of patients with allergic rhinitis, may also pos sess antiinflammatory properties. The mechanisms underlying this prope rty, however, are not clearly understood, We have cultured epithelial cells from nasal biopsy specimens Born 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 permea bility) and release of proinflammatory mediators from these cells. Add itionally, we have studied the effect of this drug on eosinophil chemo taxis 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 bead s significantly decreased the electrical resistance of these cultures, an effect that was abrogated bf treatment of the cultures with 10(-9) to 10(-3) mol/L, fexofenadine. Similarly, incubation of HNEC in tile presence of eosinophils treated with latex: beads also significantly i ncreased the basal release of the chemokine ''regulated upon activatio n, normal T cell ex pressed and secreted'' (RANTES) (from 96.0 to 613. 0 fg/mu g cellular protein; p < 0.05), IL-8 (from 42.0 to 198.5 pg/mu g cellular protein; p < 0.05), granulocyte-macrophage colony-stimulati ng factor (GM-CSF) (from 0.54 to 3.4 pg/mu g cellular protein: p < 0.0 5), and soluble intercellular adhesion molecole-1 (sICAM-1) from 7.5 t o 18.4 pg/mu g cellular protein; p < 0.05) from HNEC. The eosinophil-i nduced release of PL-S, GM-CSF, and sICAM-1 from the HNEC was signific antly attenuated by treatment with fexofenadine. Analysis of the effec ts of conditioned medium from HNEC demonstrated that this significantl y increased both eosinophil chemotaxis and adherence to endothelial ce lls. Addition of 10(-6) to 10(-3) mol/L fexofenadine to the conditione d medium significantly attenuated eosinophil chemotaxis and adherence to endothelial cells. These results suggest that fexofenadine may redu ce nasal inflammation by modulating the release of proinflammatory med iators and adhesion molecules from HNEC.