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Islets are particularly vulnerable in the initial days after transplantation when cell death results in the loss of more than half of the transplanted islet tissue. To determine whether a non-specific inflammation at the grafted site mediated by the local expression of inflammatory cytokines could play a role on the initial damage to transplanted islets, we studied the expressions of interleukin-1beta (IL-1beta) and inducible form of nitric oxide synthase (iNOS) after syngeneic islet transplantation. Insulin-treated streptozotocin-diabetic Lewis rats were syngeneically transplanted with 500 islets. Grafts were harvested 1, 3, or 7 days after transplantation, and the expressions of IL-1beta and iNOS genes were determined by RT-PCR. IL-1beta and iNOS mRNAs were detected in islets immediately after isolation, and were upregulated after transplantation. IL-1beta mRNA was ninefold increased on day 1, was still sevenfold increased on day 3 after transplantation, and declined towards pretransplantation levels on day 7. iNOS mRNA showed a similar pattern of expression to that of IL-1beta: on days 1 and 3 after transplantation it was 14-and 4-fold higher respectively than in freshly isolated islets. In addition, IL-1beta and iNOS were identified in islet grafts and found to be produced mainly by CD68-positive macrophages. A low number of IL-1beta- and iNOS-positive but CD68-negative cells were also identified suggesting that other cell types, in addition to macrophages, were involved in the expression of IL-1beta and NO production in islet grafts. The finding of increased IL-1beta and iNOS gene expressions in the initial days after islet transplantation and the presence of IL-beta and iNOS proteins in the graft confirmed the presence of an early non-specific inflammatory response after islet transplantation. Overall, the data suggest that IL-1beta plays a role in the extensive beta-cell death found in the initial days after islet transplantation.

Interleukin-1β and inducible form of nitric oxide synthase expression in early syngeneic islet transplantation