Preoperative administration of FTY720 prolonged renal allograft survival.
BACKGROUND
FTY729 is an immunomodulator obtained by chemical modification of Myriocin(ISI-1) which exists in the culture filtrate of an ascomycete, Isaria sinclairii. It has been reported that postoperative administration of FTY720 prolonged survival of various kinds of transplanted organs. In the present study, we evaluated the effect of 2-day preoperative administration of FTY 720 on graft survival.


METHODS
We used a rat renal transplantation model in which Wistar King Aptekman Hokkaido (WKAH, RT1K) served as the organ donor and Lewis (LEW, RTl) as the recipient. FTY720 was given to the recipients consecutively 2 days (day-2, day-1) before transplantation at the doses of 1, 3 or 5 mg/kg/day. Renal allograft survivals, hematological parameters of recipient blood and phenotypic analysis of recipient splenic cells and graft infiltrate were evaluated.


RESULTS
Consecutive 2-day preoperative oral administration of FTY 720 at the doses of 1, 3 or 5 mg/kg/day significantly prolonged WKAH allograft survivals compared with those of the untreated recipients. The number of peripheral blood lymphocytes was markedly decreased in the recipients treated with FTY720 at the doses of 3 mg/kg/day or 5 mg/kg/day on the 5th postoperative day. Preoperative FTY 720 administration significantly decreased the number of CD4 positive cells and the percentage of interleukin 2 receptor (IL-2 R) positive cells infiltrating both spleen and allograft at the dose of 3 mg/kg/day or 5 mg/kg/day.


CONCLUSIONS
FTY 720 could act as a safe and potent immunomodulator by decreasing the number of peripheral lymphocytes, especially CD4 positive cells and IL-2R positive cells when it is given to the recipient preoperatively.
Ueda
Haruhiko
H
Department of Urology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. uro002@poh.osaka-med.ac.jp
Takahara
Shiro
S
Itoh
Susumu
S
Nomi
Hayahito
H
Shibahara
Nobuhisa
N
Katsuoka
Yoji
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D007962:Leukocytes / Q000276:immunology; D008297:Male; D011300:Preoperative Care; D011409:Propylene Glycols / Q000276:immunology / Q000627:therapeutic use*; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D015375:Receptors, Interleukin-2; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine