Inhibition of endotoxin- and antigen-induced airway inflammation by fudosteine, a mucoactive agent

Abstract

We evaluated the effect of a mucoactive agent (−)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid (fudosteine), on airway inflammation using endotoxin- and antigen-induced models. Time courses of growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) production, neutrophil migration and goblet cell hyperplasia were examined in endotoxin-induced rat airway inflammation. GRO/CINC-1 in bronchoalveolar lavage fluid (BALF) increased in response to intratracheal instillation of endotoxin and peaked within 4h. Neutrophils in BALF and goblet cells on trachea peaked 24 and 96h after endotoxin instillation, respectively. Fudosteine significantly inhibited increases in GRO/CINC-1 at 10–100mg/kg, and neutrophils and goblet cells at 30 and 100mg/kg. These results suggest that inflammatory events including neutrophil chemoattractant production and neutrophil migration play important roles for goblet cell hyperplasia in endotoxin-induced airway inflammation, and fudosteine inhibits goblet cell hyperplasia by inhibiting GRO/CINC-1 production and/or neutrophil migration. Furthermore, fudosteine (100mg/kg) inhibited ovalbumin-induced eosinophil infiltration into BALF, suggesting it attenuates asthmatic inflammation.