Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. II. Further studies on connective tissue changes

Pulmonary fibrosis induced by bleomycin is associated with accumulation of collagen and elastin in the lungs. The excess connective tissue proteins persist despite resolution of inflammation after cessation of treatment. In the present study, mild lung injury was produced in 9 juvenile baboons by twice-weekly injections of bleomycin to a total dose of 66 units/kg. Treated animals showed losses in body weight, lung volume, and diffusing capacity. Right middle lobectomies were performed in 3 animals shortly after cessation of bleomycin. Only minimal histologic changes were present, but lobar connective tissue protein concentrations and the rate of collagen synthesis were increased. Biopsies obtained in 3 additional animals 3 months later revealed similar changes. All animals were killed 6 months after cessation of treatment. Mild fibrosis was present, and lobar contents of collagen and elastin, as well as synthetic rates of collagen and elastin, remained elevated. Accumulation of lung connective tissue proteins in this model was associated with increased rates of synthesis that persisted after discontinuance of the drug.