RRC ID 150
著者 Takahashi M, Shimizu H, Murakami T, Enosawa S, Suzuki C, Takeno Y, Hakamata Y, Kudou S, Izawa S, Yasue T, Kobayashi E.
タイトル A novel immunomodulator KRP-203 combined with cyclosporine prolonged graft survival and abrogated transplant vasculopathy in rat heart allografts.
ジャーナル Transplant Proc
Abstract To find more effective and less toxic immunosuppressive strategies in long-term treatment for organ transplantation patients, we examined the effects on rat heart allograft survival of a novel sphigosine-1-phosphate receptor agonist, KRP-203, combined with a subtherapeutic dose of cyclosporine (CsA). Rat heart transplantation was performed across a major histocompatibility complex-incompatible (DA to LEW) rat combination. KRP-203 alone showed little or no effect on heart allograft survival. In contrast, KRP-203 combined with a subtherapeutic dose of CsA led to prolonged allograft survival. Histologic analyses showed that the combination completely suppressed acute rejection, as characterized by allograft vasculopathy, mononuclear cell infiltration, and myocardial necrosis in the heart allografts. RT-PCR analysis showed that the allografts treated with CsA or KRP-203 alone showed no suppression of IL-10, IFN-gamma, and TNF-alpha mRNA expression, but when combined with a subtherapeutic dose of CsA it completely suppressed their mRNA expressions. Furthermore, the combination treatment reduced donor-specific antibody production. KRP-203 combined with a subtherapeutic dose of CsA synergistically prolonged rat heart allograft survival. The combination of CsA with KRP-203 may provide an option to prevent allograft rejection and reduce adverse effects.
巻・号 37(1)
ページ 143-5
公開日 2005-1-1
DOI 10.1016/j.transproceed.2004.12.107
PII S0041-1345(04)01546-5
PMID 15808575
MeSH Animals Cyclosporine / therapeutic use* Cytokines / genetics Drug Therapy, Combination Graft Survival / drug effects Graft Survival / immunology* Heart Transplantation / immunology* Histocompatibility Testing Immunosuppressive Agents / therapeutic use* Major Histocompatibility Complex Male Postoperative Complications / pathology* Postoperative Complications / prevention & control Rats Rats, Inbred Lew Rats, Inbred Strains Reverse Transcriptase Polymerase Chain Reaction Sulfhydryl Compounds / therapeutic use* Transplantation, Homologous / immunology
IF 0.784
引用数 11
WOS 分野 SURGERY TRANSPLANTATION IMMUNOLOGY
リソース情報
ラット