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Graft, Vol. 5, No. 3, 145-148 (2002)
DOI: 10.1177/1522162802005003006
© 2002 SAGE Publications

Differential Effects of FTY720, RAD, and CsA on Signs of Chronic Rejection in the Rat Tracheal Allograft Model

Gisbert Weckbecker

Valerie Caballero

Mireille Court

Catherine Cannet

Paul-Georg Germann

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

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