Improved outcomes of islet autotransplant after total pancreatectomy by combined blockade of IL‐1β and TNFα |
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| Authors: | B. Naziruddin M. A. Kanak C. A. Chang M. Takita M. C. Lawrence A. R. Dennison N. Onaca M. F. Levy |
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| Affiliation: | 1. Baylor Annette C. and Harold C. Simmons Transplant Institute, Dallas, TX, USA;2. Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA;3. Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA;4. Institute of Biomedical Studies, Baylor University, Waco, TX, USA;5. Department of Hepatobiliary and Pancreatic Surgery, University Hospital of Leicester, Leicester, UK |
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| Abstract: | The efficacy of islet transplant is compromised by a significant loss of islet mass posttransplant due to an innate inflammatory reaction. We report the use of a combination of etanercept and anakinra (ANA+ETA) to block inflammatory islet damage in 100 patients undergoing total pancreatectomy with islet autotransplant. The patients were divided into 3 groups: no treatment (control [CTL]), etanercept alone (ETA), or a combination of etanercept and anakinra (ANA+ETA). Peritransplant serum samples were analyzed for protein markers of islet damage and for inflammatory cytokines. Graft function was assessed by fasting blood glucose, basal C‐peptide, secretory unit of islet transplant objects (SUITO) index, and hemoglobin A1c. Administration of both antiinflammatory drugs was well tolerated without any major adverse events. Reductions in interleukin‐6, interleukin‐8, and monocyte chemoattractant protein 1 were observed in patients receiving ANA+ETA compared with the CTL group, while also showing a modest improvement in islet function as assessed by basal C‐peptide, glucose, hemoglobin A1c, and SUITO index but without differences in insulin dose. These results suggest that double cytokine blockade (ANA+ETA) reduces peritransplant islet damage due to nonspecific inflammation and may represent a promising strategy to improve islet engraftment, leading to better transplant outcomes. |
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| Keywords: | autotransplantation clinical research/practice innate immunity islet transplantation islets of Langerhans translational research/science |
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