Peritransplant and long-term secretion of interleukin-1 beta in cyclosporine treated syngeneic rats allografted with islets of Langerhans

Abstract

Interleukin-1 beta (IL-1 beta) is one of the proinflammatory cytokines that may mediate primary nonfunction of islets of Langerhans, limiting the success of allogeneic transplantation. The aim of this study was to assess differences between the secretion of IL-1 beta as well as glycemia in periand long-term periods of intraportal islet allo-transplantation with or without cyclosporine (CyA) immunosuppression. Inbred Wistar albino rats were transplanted intraportally with rat islets isolated by collagenase digestion. The two recipient groups (6 rats/group) were: group 1, control, islet transplantation (ITX) without any treatment and group 2, CyA-treated via the femoral muscle on days -1, 0, +1, and +2. Serum IL-1 beta (pg/mL) levels were measured by ELISA on days 0 (pre-ITX), +1, +2, and + 195. Tail vein blood was used to evaluate glycemia (mg/dL). No major differences were observed in IL-1 beta secretion on days 0, +1, or +195 between the groups. Immunosuppressive treatment produced significantly lower secretion in group 2 (P <.002) on day +2. Significantly greater secretions were detected at days + 195, + 1, and +195 compared to days 0, +2, and +2, respectively (P <.002;P <.008;P <.002). Positive correlations were observed between IL-1 beta levels on days +1 and +2 (r = 0.845,P <.034). The mean values in groups 1 and 2 on days 0, + 1, and +2 were 140.6 +/- 4.62 vs 119.1 +/- 12.12, 73.1 +/- 19.59 vs 88.3 +/- 14.08, 106.5 +/- 13.79 vs 92.5 +/- 15.8, respectively. No animal in group 1 displayed glycemia while three group 2 animals did at day +195. However, a negative correlation was found between IL-1 beta on day 0 and glycemia on day +195 (r = -0.999, P <.026). Our results suggest that IL-1 beta secretion, which is detrimental for islet engraftment, decreases at peritransplant day +2, but is upregulated during long-term graft survival both in controls and in CyA-treated recipients.