Bleomycin-induced pulmonary fibrosis. Effects of steroid on lung collagen metabolism.

Using bleomycin-induced pulmonary fibrosis as a model, we have set out to study collagen metabolism in the fibrotic process. As was previously shown, intratracheal administration of bleomycin in the rat caused increased deposition and net synthesis of collagen in the lung. This was accompanied by marked increases in the tissue-free proline pool size and less dramatic increases in the pool's radioactivity when lung mince was pulsed with radioactive proline to measure the net collagen synthesis. Using a technique based on the quantitation of the rate of release of hydroxyproline-containing peptides when lung homogenates were incubated in calcium-containing buffer, lung collagenolytic activity was markedly diminished as a result of bleomycin treatment. Concomitant treatment with the steroid methylprednisolone did not affect significantly this decrease in lung collagenolytic activity. Such steroid treatment, however, prevented the increase in bleomycin-induced lung collagen deposition and partially suppressed total lung collagen synthesis, without affecting the net rate of lung collagen synthesis expressed per mg of DNA. Steroid treatment also inhibited the marked increase in tissue-free proline pool size and radioactivity caused by bleomycin. The mechanism of amelioration of the fibrotic response by the steroid is discussed.