15-DEOXYSPERGUALIN PROLONGS PANCREATIC-ISLET ALLOGRAFT AND XENOGRAFT SURVIVAL IN MICE

The new immunosuppressant 15-deoxyspergualin was evaluated in allogene ic and xenogeneic pancreatic islet transplantation. In the allograft s tudy 500 collagenase-isolated C57BL/6 mouse islets were transplanted u nder the renal capsule of alloxan-diabetic C57BL/Ks mice that were eit her 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 1 5 animals were normoglycaemic one week after transplantation and 6 wer e still normoglycaemic after ten weeks, All 8 control animals were hyp erglycaemic 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 506-750 foetal porcine islet-like cell clusters. The grafts were examined for evidence of re jection with light microscopy at different time points after implantat ion. In the control animals given saline only (n=37) there was progres sive evidence of rejection starting on day seven. In 15-deoxysperguali n treated animals (2.5 mg/kg intraperitoneally; n=27) there was signif icantly less infiltration at days 7, 14 and 21. After 32 days there wa s, however, no difference between controls and 15-deoxyspergualin trea ted mice. A doubling of the 15-deoxyspergualin dose (5.0 mg/kg intrape ritoneally; n=5) did not further improve the survival of the xenograft ed islet-like cell clusters. There was no synergistic effect when cycl osporine A (12.5 mg/kg intraperitoneally) was added to the 15-deoxyspe rgualin therapy (n=34). Cyclosporine A in itself wag inefficient (n=5) in protecting the xenograft from rejection. Thus, 15-deoxyspergualin treatment induced marked prolongation of graft survival in an allogene ic adult islet transplant model (mouse to mouse) and delayed rejection in a foetal xenogeneic (pig to mouse) islet transplant model.