EFFECT OF TOPICAL ANTIINFLAMMATORY DRUGS ON EPITHELIAL CELL-INDUCED EOSINOPHIL SURVIVAL AND GM-CSF SECRETION

Topical anti-inflammatory drugs decrease eosinophil infiltration, This action may be due to an effect on the release of epithelial cell prod ucts responsible for promoting eosinophil survival. We investigated th e effect of fluticasone propionate, budesonide, beclomethasone dipropi onate and nedocromil sodium on the release of granulocyte/macrophage c olony-stimulating factor (GM-CSF) and on eosinophil survival induced b y secretions from cultured nasal epithelial cells. Human epithelial ce ll-conditioned media (HECM) were generated by cultured epithelial cell s obtained from healthy subjects undergoing corrective nasal surgery, Normodense eosinophils isolated from peripheral blood were incubated w ith HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluti casone propionate had the highest inhibitory potency (25% inhibitory c oncentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(- 8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium (IC25 5x10(-6) M). Likewise, fluticasone was the strongest ste roid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 1.3x1 0(-8) M), and nedocromil sodium (IC25 >10(-5) M), A significant correl ation was found between both inhibitory effects (r=-0.955; p<0.05). To pical anti-inflammatory drugs may decrease eosinophil survival by abro gating the promoting effect of epithelial cells, These drugs may exert part of their therapeutic effect by modulating GM-CSF release, The fo llowing rank of potency was observed: fluticasone propionate > budeson ide > beclomethasone dipropionate > nedocromil sodium, The study of th e interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.