FTY720, a new immunosuppressant, as rescue therapy in mouse cardiac transplantation.
OBJECTIVE
FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induces long-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present study investigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a mouse heterotopic cardiac transplantation model.


METHODS
BALB/c hearts were heterotopically grafted in C57BL/6 mice. FTY720, at the doses of 0.5, 1, and 5 mg.kg-1.d-1 or vehicle was administered to recipients once daily by oral gavage from d 3 to d 7 after transplantation. Histological changes of grafts, and the lymphocyte number in the peripheral blood and the peripheral lymph nodes were determined on d 5 after transplantation.


RESULTS
FTY720 prolonged the median graft survival time dose-dependently and significantly. Histological evaluation revealed less lymphocytic infiltration in cardiac allografts treated with FTY720. Moreover, FTY720 remarkably lowered the number of peripheral blood lymphocytes but significantly increased the lymphocyte number in the mesenteric lymph nodes and the peripheral lymph nodes.


CONCLUSIONS
FTY720 used orally as rescue therapy significantly extended allograft survival in mouse heterotopic cardiac transplantation.
Wang
Ming-Hui
MH
Department of Nephrology, Essen University Hospital, Essen (45122), Germany. wangminghui01@hotmail.com
Milekhin
Vitaliy
V
Zhang
Hua
H
Huang
Hong-Zheng
HZ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine