An investigation of possible models for the production of progressive pulmonary fibrosis in the rat. The effects of repeated intratracheal instillation of bleomycin.

Pulmonary fibrosis is a common later sequel to damage to the lung caused by a wide variety of agents. Bleomycin is an antineoplastic drug used in the treatment of squamous cell carcinomas and lymphomas. It is known to cause pulmonary fibrosis is both man and experimental animals. Bleomycin, dissolved in saline, was given by intratracheal instillation (dose = 0.5 U/animal; dose vol. = 0.5 ml/animal) to groups of at least 5 rats. Groups received either a single dose or 2, 3 or 4 doses each given a week apart. They were then sacrificed at periods of up to 90 days after the last dose. Subsequent histology revealed varying degrees of alveolitis, type II pneumocyte hyperplasia, alterations to alveolar structure including obliteration, degeneration, collapse and enlargement with significant interstitial fibrosis. The lesion appeared to be diffusely distributed throughout the lung. After a single dose or 2 doses regression of the lesion was observed with time following dosing whereas with 3 or 4 doses of bleomycin the changes increased progressively in extent and severity. Three or more doses of intratracheal instilled bleomycin appear to be a good model of progressive pulmonary fibrosis in the rat.