Interleukin-10 gene transfection of donor pancreas grafts protects against rejection after heterotopic pancreas transplantation in a rat model.

ABSTRACT

OBJECTIVE: The aim of this study was to assess the effect of immunoregulatory cytokine interleukin-10 (IL-10) gene therapy on pancreas tissue rejection in a heterotopic pancreas transplantation model. BACKGROUND: Modulation of inflammatory responses by anti-inflammatory cytokines (e.g., IL-10) has been suggested to minimize organ rejection. In this context, modulation of cytokines using gene therapy could be a new therapeutic modality in preventing organ rejection. METHODS: The study was performed using male inbred Wistar rats as recipients and Sprague-Dawley rats as donors. 24 h before transplantation, groups of rats, named IL-10 (n = 20) and green fluorescent protein (GFP, n = 20), were injected with viral vectors Ad5CMVhIL10 or Ad5CMVGFP. Sham-operated rats (n = 20) underwent saline injection only before transplantation. The pancreatic tissue from each of these donor rats was subsequently transplanted into the corresponding groups of streptozotocin-induced diabetic recipient rats. Recipients were thus transfected with either IL-10 (n = 20), GFP-only carrying viral vectors (n = 20) or no viral vectors (normal saline, n = 20). A selected number of animals from each recipient group (n = 5) was sacrificed at weekly intervals for 3 weeks and some were further followed up to 12 weeks before sacrifice. Histological assessment of the pancreatic tissue was made based on rejection and GFP expression. Blood glucose levels were checked daily in all groups until sacrifice. Upon sacrifice, serum cytokine and insulin levels were measured. Histopathological correlations between blood glucose levels, serum insulin levels and serum IL-10 levels were made. RESULTS: IL-10 gene therapy significantly attenuated pancreas rejection compared to controls, provided more normal blood glucose levels and elevated plasma insulin levels. Upon assumed natural deactivation of transferred viruses after 4 weeks, differences between groups in terms of rejection, blood glucose and insulin levels disappeared. CONCLUSION: These findings suggest that IL-10 gene therapy significantly reduced pancreas rejection.