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Immunosuppression and pancreatic islet transplantation
N M Kneteman1, M C Cattral, G L Warnock
1Department of Surgery, University of Alberta, Edmonton, Canada.
Hormone and Metabolic Research. Supplement Series
|January 1, 1990
Summary
Traditional immunosuppression with azathioprine and prednisone is ineffective for islet transplantation. Cyclosporine A (CsA) monotherapy shows promise but has toxicity concerns, necessitating novel approaches for successful islet engraftment.
Area of Science:
- Immunology
- Transplantation Biology
- Endocrinology
Background:
- Azathioprine-prednisone immunosuppression has failed in rodent, canine, and human islet transplantation.
- Antilymphocyte serum (ALS) shows promise in rodent models, but high-dose Cyclosporine A (CsA) monotherapy is most effective in canine islet allotransplantation.
- Nephrotoxicity limits CsA use in human islet transplantation.
Purpose of the Study:
- To evaluate the efficacy of combined immunosuppressive therapies in large animal islet allotransplantation.
- To assess the adverse effects of CsA, azathioprine, and prednisone on islet engraftment and function.
- To explore an alternative immunosuppressive strategy for clinical islet transplantation.
Main Methods:
- Investigated the impact of adding azathioprine and prednisone to CsA immunosuppression in large animal models.
- Assessed the dose-dependent effects of CsA on islet engraftment, insulin secretion, and peripheral insulin activity.
- Implemented a clinical protocol involving Minnesota antilymphocyte globulin induction, delayed CsA, and low-dose triple immunotherapy.
Main Results:
- No additional benefit was observed from adding azathioprine and prednisone to CsA in large animal islet allotransplantation.
- CsA, azathioprine, and prednisone demonstrated potential adverse effects on islet engraftment and insulin function.
- CsA's adverse effects appeared dose-related and potentially reversible.
Conclusions:
- Standard immunosuppressive regimens have limitations in islet transplantation.
- A novel clinical approach using potent induction immunosuppression with Minnesota antilymphocyte globulin, delayed CsA, and low-dose triple therapy shows encouraging initial results.
- This strategy aims to balance immunosuppression efficacy with reduced toxicity for improved islet transplantation outcomes.