Tumor Necrosis Factor-α Production by Human Islets Leads to Postisolation Cell Death

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Abstract
Background. Recent successes in islet transplantation highlight the importance of islet isolation by experienced centers and minimization of cell injury as crucial to the achievement of insulin independence. Islet injury may manifest as cell death by apoptosis, shorter graft survival, and the need for retransplantation. Although an inflammatory cytokine response at the graft site is known to inhibit engraftment, recent evidence indicates that islet cells may contribute to this response. Methods. Isolated human islets were cultured for up to one week in serum-free CMRL-1066 with 25 μM of tumor necrosis factor (TNF)α inhibitor RDP58. Gene expression was measured by reverse transcriptase polymerase chain reaction, apoptosis and TNFα secretion by enzyme-linked immunosorbent assay and enzyme-linked immunospot, and islet function by stimulated insulin secretion. Results. Isolation induced a twofold increase in TNFα expression between days one and three (PPPPPPP<0.02). Conclusions. These data demonstrate that intraislet cytokine production should be considered as a factor leading to islet cell death postisolation and postengraftment, and strategies aimed at countering islet cytokine production represent a novel target for improving islet viability and function.

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