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Prevention of graft rejection and graft-versus-host reaction by a novel immunosuppressant, FTY720, in rat small bowel transplantation. 1997

M Mitsusada, and S Suzuki, and E Kobayashi, and S Enosawa, and T Kakefuda, and M Miyata
Department of Experimental Surgery and Bioengineering, National Children's Medical Research Center, Tokyo, Japan.

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.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007421 Intestine, Small The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM. Small Intestine,Intestines, Small,Small Intestines
D011409 Propylene Glycols Derivatives of propylene glycol (1,2-propanediol). They are used as humectants and solvents in pharmaceutical preparations. Propanediols,Glycols, Propylene
D011917 Rats, Inbred Lew An inbred strain of rat that is used in BIOMEDICAL RESEARCH. Rats, Inbred Lewis,Rats, Lew,Inbred Lew Rat,Inbred Lew Rats,Inbred Lewis Rats,Lew Rat,Lew Rat, Inbred,Lew Rats,Lew Rats, Inbred,Lewis Rats, Inbred,Rat, Inbred Lew,Rat, Lew
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections
D006087 Graft vs Host Reaction An immunological attack mounted by a graft against the host because of HISTOINCOMPATIBILITY when immunologically competent cells are transplanted to an immunologically incompetent host; the resulting clinical picture is that of GRAFT VS HOST DISEASE. HLA Sensitization,Human Leukocyte Antigen Sensitization,Sensitization, HLA
D000068876 Fingolimod Hydrochloride A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS. 2-Amino-2-(2-(4-octylphenyl)ethyl)-1,3-propanediol hydrochloride,FTY 720,FTY-720,FTY720,Fingolimod,Gilenia,Gilenya
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013110 Sphingosine An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed) 4-Sphingenine,4 Sphingenine
D016572 Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). Cyclosporin A,Ciclosporin,CsA-Neoral,CyA-NOF,Cyclosporin,Cyclosporine A,Neoral,OL 27-400,Sandimmun,Sandimmun Neoral,Sandimmune,CsA Neoral,CsANeoral,CyA NOF,OL 27 400,OL 27400

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