Modification of the pulmonary connective tissue developmental response in the neonatal rat by ciclosporin

Neonatal rat pups were treated either with ciclosporin at 10 mg/kg/day dissolved in olive oil (experimental) or with pure olive oil (control). Lung protein biosynthesis was evaluated in a protocol which involved the measurement of total accumulated protein, collagen and elastin. Four time points were studied in the first 21 days of life, 12 animals contributing to each point (6 control and 6 ciclosporin). Ciclosporin levels in the treated group ranged widely (2,000-4,000 ng/ml). There were significant differences in total body weight and lung weight in treated vs. controls during and after the first week. DNA contents per unit wet weight varied significantly during the second week of life, indicating increased cellularity of the ciclosporin-treated animals. Associated with this was an increase in the lung protein/DNA ratio as well as the elastin/DNA ratio in the control animals, but not in the treated ones. The lung collagen/DNA ratio was not as dramatically affected by the ciclosporin treatment. However, the collagen content per unit wet weight of lung tissue was increased in the ciclosporin-treated animals at 15 days of life. We conclude that ciclosporin has a marked effect on lung connective tissue metabolism in early life, the long-term effects of which are unappreciated and undocumented but may well be of vital importance in the lungs of long-surviving organ transplant patients.