Effects of cyclophosphamide treatment in experimental asbestosis

The potential role of immunosuppressive therapy in asbestosis was evaluated in the sheep model of experimental asbestosis. A diffuse peribronchiolar alveolar and interstitial fibrosing alveolitis was developed in 10 animals following 2 years of exposure consisting of slow intratracheal infusion of 100 mg Canadian chrysotile in 100 ml saline every 2 weeks. A control group of 10 sheep concomitantly receiving only 100 ml saline intratracheally was also enrolled in the study. One group of 5 control sheep and one group of 5 asbestosis sheep received 1 mg/kg cyclophosphamide in 10 ml saline iv every 2 weeks, the other 10 sheep receiving only saline. One year after beginning of therapy, survival rates were comparable in the 2 control groups and the asbestosis group without therapy at 80%, whereas it was significantly reduced at 20% in the asbestosis group with therapy. Deaths in the latter were associated with significant increase in peripheral blood and lung lavage neutrophils, increased intensity of fibrosing alveolitis, worsening of lung functions, and worsening in the radiographic diffuse lung opacities. This was documented on histopathology to be associated with more intense fibrotic disease and bacterial pneumonia in the group of sheep with asbestosis receiving the immunosuppressor drug. We conclude that cyclophosphamide therapy in experimental asbestosis accelerated the fibrotic process and reduced significantly the survival rate of the animals.