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Pulm Pharmacol Ther. 2005;18(2):121-7. Epub 2004 Dec 20.

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

Author information

1
Research Laboratory III, Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033, Japan. komatsu.hirotsugu@mc.m-pharma.co.jp

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 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.

PMID:
15649854
DOI:
10.1016/j.pupt.2004.11.002
[Indexed for MEDLINE]

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