Open AccessEffect of peritransplant FTY720 alone or in combination with post‐transplant tacrolimus in a rat model of cardiac allotransplantation
Author(s) -
Xu Min,
Pirenne Jacques,
Antoniou Efstathios A,
Afford Simon C,
D'Silva Milbhor,
McMaster Paul
Publication year - 1998
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.1998.tb00973.x
Subject(s) - tacrolimus , allotransplantation , medicine , cd8 , population , lymphocyte , kidney , immunosuppression , pharmacology , transplantation , immunology , immune system , environmental health
FTY720 is a recently discovered compound that is derived from the fungus Isaria sinclairii. Using a DA donor‐to‐LEW recipient rat combination, we assessed the efficacy of peritransplant FTY720 alone or in combination with post‐transplant tacrolimus on the survival of cardiac allografts. Peritransplant FTY720 given orally at a dose of 5 mg/kg on days ‐1 and 0 prolonged graft survival from 5 to 13 days ( P < 0.05). Combining peritransplant FTY720 with post‐transplant tacrolimus resulted in a further prolongation of allograft survival. The lymphocyte count in transplanted rats decreased within 24 h to 46.6 %. Analysis of lymphocyte subsets by FACS revealed that FTY720 affected the total population of CD3‐bearing T cells while the ratio of CD4 to CD8 cells remained unchanged. Kidney and liver biochemistry remained elevated for 2 weeks. In conclusion, FTY720 is a powerful immunosuppressive agent when used as induction therapy and may have an additive effect ‐ perhaps a synergistic one ‐ with post‐transplant tacrolimus.