Prevention of graft rejection and graft-versus-host reaction by a novel immunosuppressant, FTY720, in rat small bowel transplantation.
In the present study, we examined the immunosuppressive effect of a new drug, FTY720, on small bowel transplantation (SBT) in rats. Grafts from (LEW x BN) F1-to-LEW rats treated with FTY720 at 0.5 mg/kg from day 0 to 14 post-SBT survived significantly longer than untreated grafts. In addition, the administration of FTY720 combined with cyclosporin (CyA; 5 mg/kg per day) had a synergistic effect on allograft survival. The graft-versus-host reaction (GVHR) that occurred in the LEW-to-F1 rats was markedly reduced after the administration of FTY720. FTY720 combined with a low dose of CyA completely abrogated GVHR without any adverse reaction. FTY720 treatment resulted in a significant decrease in the number of lymphocytes in the peripheral blood and the spleen, but the number of peripheral neutrophils was unchanged. Thus, FTY720 would appear to be an ideal drug to combine with CyA in order to control the immune reaction after SBT.
Mitsusada
M
M
Department of Experimental Surgery and Bioengineering, National Children's Medical Research Center, Tokyo, Japan.
Suzuki
S
S
Kobayashi
E
E
Enosawa
S
S
Kakefuda
T
T
Miyata
M
M
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000517:prevention & control*; D006087:Graft vs Host Reaction / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000637:transplantation*; D018655:Lymphocyte Count / Q000187:drug effects; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine