Modulation of HLA-DR antigen and ICAM-1 molecule expression on airway epithelial cells by sodium nedocromil

Objective: To test in vitro and in vivo the hypothesis that sodium nedocrom il could modulate the expression of surface molecules on airway epithelial cells. M ethods: Human bronchial epithelial cells, obtained from surgically resected bronchi, were cultured and stimulated with recombinant IFN-gamma in the pr esence of sodium nedocromil. The intensity of the expression of surface mol ecules HLA-DR and ICAM-1 molecules on bronchial epithelial cells in vitro, was quantified by specific antibody staining and flow-cytometry analysis. F urthermore, we studied the effect of the drug on airway inflammation in viv o and on allergic rhinitis patients sensitized to house dust mites. Nasal e pithelial cells were collected by brushing, at baseline and 2 to 3 weeks af ter treatment with sodium nedocromil. The expression of HLA-DR and ICAM-1 m olecules was measured by flow-cytometry, and the proportions of neutrophils and eosinophils "contaminating" the epithelial cells evaluated by light mi croscopy examination of nasal brushings. Results: The enhanced HLA-DR and ICAM-1 expression, induced by IFN-gamma, w as effectively downregulated, in a dose-dependent manner, by sodium nedocro mil. At all the concentrations tested (10(-9) to 10(-4) M), the inhibitory activity of the drag was stronger on HLA-DR than on ICAM-1 expression (P<.0 5, all comparisons). As compared with healthy subjects, patients with aller gic rhinitis had a higher expression of HLA-DR (P<.05) but not of ICAM-1 mo lecules (P>.05) on nasal epithelial cells, and higher proportions of nasal eosinophils (P<.05). Treatment with sodium nedocromil downregulated the exp ression of HLA-DR (P<.05), but not of ICAM-1 (P>.05), and induced a mild, b ut not statistically significant, decrease of nasal eosinophilia (P>.05). Conclusion: These data demonstrate that the antiinflammatory activity of so dium nedocromil may include modulation of surface molecule expression on ai rway epithelial cells.