15-Deoxyspergualin prolongs pancreatic islet allo- and xenograft survival in mice.
The new immunosuppressant 15-deoxyspergualin was evaluated in allogeneic and xenogeneic pancreatic islet transplantation. In the allograft study 500 collagenase-isolated C57BL/6 mouse islets were transplanted under the renal capsule of alloxan-diabetic C57BL/Ks mice that were either 15-deoxyspergualin-treated (n = 15) or given saline only (n = 8). When 15-deoxyspergualin was given (5 mg/kg b.wt. intraperitoneally) until day 28 after transplantation in a special dosage schedule, 10 out of 15 animals were normoglycaemic one week after transplantation and 6 were still normoglycaemic after ten weeks. All 8 control animals were hyperglycaemic after 18 days. Light microscopy showed graft rejection in hyperglycaemic mice, but only mild infiltration of lymphocytes in the grafts of normoglycaemic animals. In the xenograft study C57BL/Ks mice were transplanted under the renal capsule with 500-750 foetal porcine islet-like cell clusters. The grafts were examined for evidence of rejection with light microscopy at different time points after implantation. In the control animals given saline only (n = 37) there was progressive evidence of rejection starting on day seven. In 15-deoxyspergualin treated animals (2.5 mg/kg intraperitoneally; n = 27) there was significantly less infiltration at days 7, 14 and 21. After 32 days there was, however, no difference between controls and 15-deoxyspergualin treated mice. A doubling of the 15-deoxyspergualin dose (5.0 mg/kg intraperitoneally; n = 5) did not further improve the survival of the xenografted islet-like cell clusters. There was no synergistic effect when cyclosporine A (12.5 mg/kg intraperitoneally) was added to the 15-deoxyspergualin therapy (n = 34).(ABSTRACT TRUNCATED AT 250 WORDS)
Sandberg
J O
JO
Department of Medical Cell Biology, Uppsala University, Sweden.
Korsgren
O
O
Groth
C G
CG
Andersson
A
A
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus