[Immunosuppressive effect in combination therapy of cyclosporine A, FK506 and 15-deoxyspergualin on a pancreatic islet xenotransplantation].
The purpose of this study was to investigate the immunosuppressive effect of Cyclosporine A (CsA), FK506 (FK) and 15-Deoxyspergualin (DSG) on pancreatic islet xenotransplantation (hamster to rat). Mean graft survival time of control was 2.9 +/- 0.6 days. CsA of 20mg/kg/day, FK of 0.5mg/kg/day and DSG of 1mg/kg/day prolonged graft survival to 6.2 +/- 2.0, 6.4 +/- 1.6 and 5.2 +/- 1.9 days, respectively. In combination of CsA with FK, graft survival time was 12.9 +/- 6.3 days, DSG combined with CsA, and DSG combined with FK could significantly prolong graft survival in synergistic fashion to 31.4 +/- 13.2 days and 30.7 +/- 6.5 days, respectively. Triple combination of these three drugs could not prolong graft survival more than double combination. Lymphocytotoxic antibody titer rose after grafting in single use of CsA, FK and DSG, but any combination therapy completely suppressed production of lymphocytotoxic antibody. Histologically, CsA combined with FK eliminated medullary thymocytes, but not cortical thymocytes. On the other hand, DSG combined with CsA or FK eliminated both of medullary and cortical thymocytes. In conclusion, CsA and FK may have similar immunosuppressive mode of action different from that of DSG. Combination therapy of DSG with CsA or FK could significantly prolong islet xenograft survival.
Ueno
M
M
First Department of Surgery, Nara Medical University, Japan.
Nakajima
Y
Y
Kanehiro
H
H
Yoshimura
A
A
Nakano
H
H
D000818:Animals; D000961:Antilymphocyte Serum / Q000097:blood; D006224:Cricetinae; D016572:Cyclosporine / Q000008:administration & dosage* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000187:drug effects*; D006146:Guanidines / Q000008:administration & dosage* / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016381:Islets of Langerhans Transplantation; D008297:Male; D008647:Mesocricetus; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology; D013950:Thymus Gland / Q000473:pathology; D014183:Transplantation, Heterologous
D000961:Antilymphocyte Serum; D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus; D016559:Tacrolimus