Collagen synthesis and degradation in acutely damaged mouse lung tissue following treatment with prednisolone

Abstract

Corticosteroids are widely used to treat patients with acute lung damage. Recent work has shown that the administration of 30 mg/kg prednisolone to mice, twice daily on days 1–5 after the induction of lung damage with butylated hydroxytoluene (BHT), results in the development of a more severe fibrotic lesion [J.P. Kehrer, A.J.P. Klein-Szanto, E.M.B. Sorensen, R. Pearlman and M.H. Rosner, Am. Rev. resp. Dis. 130, 256 (1984)]. In the present study, the rate of collagen synthesis in lung tissue from BHT-saline-treated mice was greater than that in lung tissue from oil-treated controls at all days examined. During prednisolone treatment, the rate of pulmonary collagen synthesis was significantly less in tissue from BHT-prednisolone-treated mice compared to BHT-saline controls. Two days after steroid treatment was stopped (day 7 after BHT), there was a significant increase in the rate of collagen synthesis in lung tissue from BHT-prednisolone-treated mice compared to tissue from both BHT- and oil-treated controls. This increase reached a maximum on day 11 and persisted to day 14 after BHT. The rate of pulmonary non-collagen protein synthesis was inconsistently increased in response to treatments with BHT and/or prednisolone. There was, therefore, a relatively greater increase in the synthesis of collagen. The percentage of total protein synthesis committed to collagen increased from 2% in oil-treated controls to 5% on day 7 after BHT alone and reached a maximum of 7.1% on day 11 in lung tissue from BHT-prednisolone-treated mice. The percentage of newly synthesized collagen that was degraded in lung tissue from BHT-prednisolone-treated mice was significantly lower than BHT-saline on days 7 and 11, and lower than oil-prednisolone on day 14. These results show that collagen synthesis was decreased in BHT-damaged mouse lung tissue during short-term, high-dose steroid therapy. There was, however, an increase in collagen synthesis and a decrease in the degradation of newly synthesized collagen after steroid therapy was stopped. These changes in collagen metabolism may contribute to the steroid-induced enhancement of fibrosis seen in BHT-treated mice.