The IL-1 Receptor Antagonist Anakinra Enhances Survival and Function of Human Islets during Culture: Implications in Clinical Islet Transplantation

Abstract Objectives Human islet transplantation provides a feasible approach for treatment of type 1 diabetes mellitus but is limited by insufficient pancreatic donors and islet loss during pretransplant culture and posttransplantation. We examined if treatment with Anakinra (Kineret), a clinically approved interleukin-1 (IL-1) receptor antagonist, enhances survival and/or function of human islets during culture as a potential approach to improve the quality and quantity of islets for transplantation. Methods Isolated human islets (n=5 donors) were cultured with or without Anakinra. Islet function, β-cell area, apoptosis, β/α-cell ratio and IL-1β release were assessed by glucose stimulated insulin secretion, quantitative immunolabelling and enzyme-linked immunosorbent assay. Results β-cell apoptosis increased during islet culture in a time-dependent manner (D0: 1.9 ± 0.4%, D2: 4.4 ± 0.4%, D4: 6.1 ± 0.7%) that was associated with increased islet IL-1β release, decreased islet β-cell area (D0: 72 ± 4.9% vs. D4: 55 ± 6.3%; % islet area) and β/α-cell ratio (D2: 2.3 ± 0.3, D4: 1.7 ± 0.2). Anakinra-treated islets had markedly lower β-cell apoptosis (D2(+An): 2.4 ± 0.4, D4(+An): 3.1 ± 0.6%), higher islet β-cell area (D4(+An): 69 ± 3.8%) and β/α-cell ratio (D4(+An): 2.1 ± 0.15) than nontreated cultured islets (p Conclusions Blocking IL-1 receptor with Anakinra protects cultured human islets from IL-1β-mediated β-cell dysfunction and apoptosis. IL-1 receptor blockers may provide a new approach to enhance islet survival and function during pretransplant culture thereby increase the success rate of islet transplantation.