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

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 4 h. Neutrophils in BALF and goblet cells on trachea peaked 24 and 96 h after endotoxin instillation, respectively. Fudosteine significantly inhibited increases in GRO/CINC-1 at 10-100 mg/kg, and neutrophils and goblet cells at 30 and 100 mg/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 (100 mg/kg) inhibited ovalbumin-induced eosinophil infiltration into BALF, suggesting it attenuates asthmatic inflammation.