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

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 nonspecific 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 inrerleukin-1 beta (IL-1 beta) and inducible form of nitric oxide sviithase (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-1 beta and WOS genes were determined by RT-PCR. IL-1 beta and iNOS mRNAs were detected in islets immediately after isolation, and were upregulated after transplantation. IL-1 beta 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-1 beta: on days 1 and 3 after transplantation it was 14 and 4-fold higher respectively than in freshly isolated islets. In addition, IL-1 beta and iNOS were identified in islet grafts and found to be produced mainly by CD68-positive macrophages. A low number of IL-1 beta- 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-1 beta and NO production in islet grafts. The finding of increased IL-1 beta 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-1 beta plays a role in the extensive beta-cell death found in the initial days after islet transplantation.