Long-term morphologic and biochemical features of experimentally induced lung fibrosis in the mouse

Mice were injected with 400 mg. per kg. of butylated hydroxytoluene (BHT) and exposed to an atmosphere of 70 per cent oxygen for 6 days. Control groups were animals treated with BHT alone or injected with vehicle and kept for 6 days in either O2 or air. Animals were killed at various time intervals after BHT treatment, and the lung changes were evaluated with biochemical and morphologic techniques. In animals exposed to BHT + O2, there was initially a diffuse interstitial pneumonitis, increased levels of interstitial collagen, and a decreased ratio of type III to type I collagen. With time the inflammatory component subsided, and degenerative changes primarily consisting of dilation of terminal airways and of alveoli became apparent. Elevated levels of lung hydroxyproline persisted until the termination of the study at 1 year, although ratios of type III to type I collagen returned to normal. In animals treated with BHT alone, collagen accumulation and morphologic changes were similar, although much less severe. It is concluded that potentiation of acute lung injury by oxygen produces long-lasting morphologic and biochemical alterations in lung parenchyma.