The human fibrotic lung disorders are a heterogeneous group of diseases characterized by changes in alveolar supporting tissue. The end stage of many diverse causes of this disorder is the fibrotic lung. Since collagen has a central role in fibrosis, we have used agents which block collagen synthesis or enhance its degradation as potential inhibitors of experimental pulmonary fibrosis. A variety of experimetnal models is providing insights into mechanisms involved in the fibrotic process. Two models used here are bleomycin-induced fibrosis in the hamster and oxygen toxicity in the rat. Both models have increased collagen content of lungs although they differ in structure and lung mechanics. We have tested two agents in these models: cis-4-hydroxy-L-proline (cis-hydroxyproline), a proline analogue which specifically inhibits collagen synthesis, and beta-amino-propionitrile, a crosslink inhibitor of collagen and elastin. Our wor has shown that both agents prevent the structural, functional, and biochemical changes of preliminary fibrosis without causing toxic side effects. Considering the effectiveness of these agents in animal models, it seems reasonable that they might be used in human trials of disorders characterized by rapid synthesis of connective tissue. Such disorders might be the adult respiratory distress syndrome, bleomycin-induced pulmonary fibrosis, radiation fibrosis, and oxygen toxicity.
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