Session: SAT 834-867-Islet Biology
Bench to Bedside
Poster Board SAT-860
Objective: To compare plasma levels and pancreatic gene expression of proinflammatory cytokines (TNF, IL-6, IL-1β and IFN-γ) and TF between brain-dead organ donors and control subjects who undergone therapeutic pancreatectomy.
Methods: This study comprised 17 brain-dead patients (cases) and 20 control patients. From each subject, it was collect an aliquot of peripheral blood and a biopsy of pancreatic tissue. Plasma TNF, IL-6, IL-1β, IFN-γ and TF were measured using commercial ELISA kits. Gene expressions of these cytokines and TF were evaluated by RT-qPCR on pancreatic tissue samples. Protein quantifications were performed by immunohistochemistry in paraffin-embedded pancreas sections.
Results: Brain-dead patients had higher plasma concentrations of TNF and IL-6 in comparison to controls [TNF: 12.3ng/ml (0.1-23.6) vs. 3.8ng/ml (3.4-6.62), P=0.02; IL6: 1127.1ng/ml (355.7-4571.6) vs. 92.8ng/ml (55.3-262.6), P<0.0001]. The groups had similar TNF, IL-6, IL-1β, and IFN-γ mRNA levels in pancreatic tissue. However, RT-qPCR revealed significant up-regulation of TF mRNA expression in control patients as compared to brain-dead patients [control 1.38-fold (0.7-2.0) vs. brain-dead 0.39-fold (0.1-1.2), P=0.037]. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls (16.81 ± 5.2 pixels vs. 11.57 ± 4.93 pixels; P<0.005), in agreement with the results obtained for plasma TNF levels (r=0.451; P=0.014). Moreover, TNF protein was widely distributed in all pancreatic tissue, including islets. IL-6 and IL-1β proteins were identified in both ductal cells and islet cells, but no significant difference was observed between cases and controls. IFN-γ and TF proteins were minimally observed in pancreatic tissue and were present with similar amounts in case and control groups.
Conclusion: BD induces inflammatory activity evidenced by the up-regulation of TNF in plasma and pancreatic tissue. Blocking the expression of key inflammatory mediators in brain-dead donors should be evaluated as a new approach to improve the outcomes of islet transplantation.
Nothing to Disclose: DC, THR, JR, SB, ABO, CBL
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