Acceleration of chronic failure of intrahepatic canine islet autografts by a short course of prednisone.
A topic of current interest in islet transplantation is the selection of an optimal site for long-term graft survival since the intrahepatic site may be characterized by long-term failure. Additionally, the use of immunosuppressive agents such as prednisone may adversely affect long-term graft function. In this study, we examined the long-term outcome of intrahepatic canine islet autografts and compared this with results obtained in animals treated with a short-term course of steroids or steroids plus insulin. Islets were isolated using the automated method and were purified on discontinuous Euro-Collins Ficoll gradients (densities: 1.108, 1.096, 1.037). Prednisone-treated dogs were hyperglycemic during treatment but returned to normoglycemia after steroid withdrawal. Control and insulin-treated animals were normoglycemic following autotransplant, with no difference in plasma glucose levels between controls and the insulin-treated animals. All control dogs became diabetic at 11, 14, 17, and 19 months following islet autograft. Prednisone-treated dogs had more rapid onset of diabetes at 7, 11, and 12 months following ITx. Prednisone-treated dogs given insulin became hyperglycemic at 10, 14, 18, and 19 months post ITx. Graft failure was preceded by a decline in IVGTT Kg values and diminished insulin secretion. At the time of graft failure islets showed no lymphocytic infiltration and islets stained positive for glucagon but few insulin-containing cells were seen. Thus, even when an initially adequate B cell mass was transplanted, the intrahepatic site was characterized by long-term canine autograft failure. A short course of prednisone accelerated the time to graft failure and insulin treatment reversed this acceleration.
Rilo
H L
HL
University of Pittsburgh Transplantation Institute, Pennsylvania 15213.
Carroll
P B
PB
Zeng
Y J
YJ
Fontes
P
P
Demetris
J
J
Ricordi
C
C
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery; D004285:Dogs; D005260:Female; D006084:Graft Rejection / Q000139:chemically induced* / Q000276:immunology; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000601:surgery; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects*; D014182:Transplantation, Autologous
D001786:Blood Glucose; D007328:Insulin; D011241:Prednisone