© 2002 SAGE Publications
Differential Effects of FTY720, RAD, and CsA on Signs of Chronic Rejection in the Rat Tracheal Allograft Model
Obliterative bronchiolitis (OB) is an unresolved issue in lung transplantation. The antirejection properties of FTY720, RAD, and cyclosporin A (CsA) were compared in the Brown-Norway to Lewis rat tracheal allograft model of OB. Using daily oral doses of 0.3, 2.5, and 7.5 mg/kg for FTY720, RAD, and CsA, respectively, the inhibition of tracheal graft rejection was studied by giving the drugs from day -3 prior to transplantation to day 3, -3 to 28, 0 to 28, 3 to 28, or 10 to 28. Grafts were removed on day 28 and processed for quantitative histology. The inhibitory effect of FTY720 on tracheal stenosis was most pronounced with the regimen day -3 to day 28 (obliteration 6.3% ± 4.1% vs 94.1% ± 3.4% in controls, mean ± SE). FTY720 (days -3 to day 28) completely prevented inflammatory cell infiltration of the graft and markedly (> 70%) decreased blood lymphocyte counts. RAD exerted strong to intermediate inhibitory action on the development of tracheal obliteration with all the treatment regimens tested (obliteration ranging from 3.2% ± 0.7% for days 0 to 28 to 57% ± 13% for days -3 to 3). CsA treatment was efficacious with the regimens -3 to 28 and 0 to 28. In conclusion, single agent regimens of the new immunosuppressants FTY720 and RAD have been identified that can prevent or inhibit signs of chronic rejection in the rat tracheal transplantation model.
Key Words: obliterative bronchiolitis FTY720 RAD cyclosporin rat lung transplantation