ROLE OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PULMONARYFIBROSIS INDUCED IN MICE BY BLEOMYCIN

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in pulmonary fibrosis elicited in mice by the intratracheal instillati on of bleomycin was investigated by (1) evaluation of GM-CSF mRNA leve ls, (2) administration of GM-CSF, and (3) administration of anti-GM-CS F antibody. A significant increase of the GM-CSF mRNA level was eviden t in the lung RNA on day 5 after bleomycin instillation, but not on da y 15. Abdominal infusion of GM-CSF (0.5 mug/h during days 7-15) did pr event the collagen deposition induced by bleomycin, as measured by the lung hydroxyproline content on day 15. In contrast, anti-GM-CSF antib ody markedly aggravated the collagen deposition. On histological secti ons the proportion of lungs showing fibrosing alveolitis was decreased by GM-CSF and increased by anti-GM-CSF IgG. The percentage and number of macrophages within the bronchoalveolar lavage (BAL) fluid was incr eased by GM-CSF infusion and decreased by anti-GM-CSF antibodies. This study demonstrates that pulmonary GM-CSF has an inhibitory influence upon the alveolar remodeling and collagen deposition associated with p ulmonary fibrosis.