Effect of peritransplant FTY720 alone or in combination with post-transplant tacrolimus in a rat model of cardiac allotransplantation.
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.
Liver Transplant and Hepatobiliary Unit, Queen Elizabeth Hospital and Medical Center, Edgbaston, Birmingham, UK.
M
M
Xu
J
J
Pirenne
E A
EA
Antoniou
S C
SC
Afford
M
M
D'Silva
P
P
McMaster
D000818:Animals; D004359:Drug Therapy, Combination; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D016559:Tacrolimus