Effect of a new immunosuppressive agent, FTY720, on survival of islet allografts.
A newly developed immunosuppressant, FTY720, has a unique mechanism that is quite different from those of conventional immunosuppressants, and is presumed to be mediated through decreases in the number of peripheral lymphocytes, especially helper T cells. This study was performed to ascertain whether this innovative drug could prolong islet allograft survival. The donors were inbred Lewis rats and the recipients were ACI rats rendered hyperglycemic with intravenous streptozotocin. In the study group, FTY720 dissolved in distilled water was orally administered at a dose of 5 mg/kg to the recipient ACI rats 1 day before and on the day of grafting. In the control group, only distilled water was orally administered to the recipient ACI rats on the day before and the day of grafting. Two thousand islets were transplanted into the portal vein of the recipient rats in the study and control groups immediately after isolation. The graft survival time in the study group was significantly longer than that in the control group, indicating that FTY720 retains a potent effect on the prolongation of islet allograft survival. FTY720 could become a useful immunosuppressant for future clinical islet allotransplantation.
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan.
T
T
Yamasaki
K
K
Inoue
H
H
Hayashi
Y
Y
Gu
H
H
Setoyama
J
J
Ida
W
W
Cui
Y
Y
Kawakami
M
M
Kogire
M
M
Imamura
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation; D008297:Male; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine