A new immunosuppressant, FTY720, prolongs limb allograft survival in rats.
A new immunosuppressant, FTY720, was applied to limb allotransplants and its effectiveness was investigated. Using inbred rats, for which the major histocompatibility complexes were completely mismatched, 31 limb transplantations were performed and FTY720 was administered at a dose of 1.5 or 3 mg per kilogram per day for 10 days postoperatively. Rejection was monitored by the appearance of the skin of the grafted hind limb, soft radiograph, microangiography, and histology. In animals receiving no immunosuppressive therapy, the mean onset of rejection was 4.2+/-1.0 days postoperatively, and the grafted limbs became acutely necrotic. The mean onset of rejection was 6.0+/-0.9 days in animals receiving FTY720 at a dose of 1.5 mg per kilogram per day and 7.9+/-1.5 days in animals receiving FTY720 at a dose of 3 mg per kilogram per day. Survival of the grafted limbs was significantly prolonged compared with that in animals without immunosuppression. The immunosuppressive effect of FTY720 appeared to be dose dependent; however, complete suppression of rejection could not be obtained with FTY720 therapy alone.
Muramatsu
K
K
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, Ube, Japan.
Doi
K
K
Shigetomi
M
M
Kido
K
K
Kawai
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000187:drug effects*; D006614:Hindlimb / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013110:Sphingosine / Q000031:analogs & derivatives; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine