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¹ Institut d’Investigació Biomèdica de Bellvitge (IDIBELL); Endocrine Unit, Hospital Universitari de Bellvitge, Barcelona, Spain
² Department of Clinical Sciences, University of Barcelona, Barcelona, Spain

(Requests for offprints should be addressed to E Montanya who is now at Endocrine Unit (13-2), Hospital Universitari Bellvitge, Feixa Llarga, s/n, 08907 L’Hospitalet de Llobregat, Barcelona, Spain; Email: montanya{at}ub.edu)

^* (M Montolio and M Biarnés contributed equally to this work)

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

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