Direct effects of corticosteroids on in vitro collagen production by normal and damaged lung tissue

The direct, short-term effects of prednisolone on the synthesis of collagen in minced lung tissue from normal mice and from mice with butylated hydroxytoluene(BHT)-induced lung damage were studied. Collagen production rates in lung tissue from BHT-treated or untreated mice were unaffected by 10 or 25 micrograms/ml prednisolone. There was a significant inhibition of collagen production rates in lung tissue from untreated mice by 50 or 100 micrograms/ml prednisolone although there was no effect on the percentage of protein synthesis committed to collagen. Prednisolone 50 and 100 micrograms/ml also inhibited the rate of collagen synthesis in lung tissue obtained 3 days after BHT but, in addition, decreased the percentage of protein synthesis committed to collagen. Seven days after BHT, prednisolone increased both the rate and percentage of pulmonary collagen synthesis. The response of lung tissue to prednisolone 11 days after BHT resembled that of tissue from untreated mice. The tissue concentrations of prednisolone following in vitro incubations were significantly lower in lung from normal compared to BHT-treated mice. These in vitro concentrations were about 100-fold higher than those measured 2 h after an in vivo dose of 30 mg/kg. There were no significant differences in lung prednisolone concentrations between normal and BHT-treated mice in vivo. These data suggest that the observed effect of corticosteroids in vitro on the synthesis and degradation of collagen in lung tissue is variable and depends on the time after an acute insult when these parameters are assessed. The concentrations of prednisolone in lung tissue required to achieve these effects in vitro were significantly greater than those achieved in vivo.