1. Brain death-induced inflammatory activity in human pancreatic tissue: a case-control study.
- Author
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Rech TH, Crispim D, Rheinheimer J, Barkan SS, Osvaldt AB, Grezzana Filho TJ, Kruel CR, Martini J, Gross JL, and Leitão CB
- Subjects
- Adult, Aged, Case-Control Studies, Female, Humans, Immunohistochemistry, Interferon-gamma analysis, Interferon-gamma genetics, Interleukin-1beta analysis, Interleukin-1beta genetics, Interleukin-6 analysis, Interleukin-6 genetics, Male, Middle Aged, Tumor Necrosis Factor-alpha analysis, Tumor Necrosis Factor-alpha genetics, Brain Death immunology, Inflammation etiology, Pancreas immunology
- Abstract
Background: Long-term insulin independence after islet transplantation depends on engraftment of a large number of islets. However, the yield of pancreatic islets from brain-dead donors is negatively affected by the up-regulation of inflammatory mediators. Brain death is also believed to increase tissue factor (TF) expression, contributing to a low rate of engraftment., Methods: We conducted a case-control study to assess brain death-induced inflammatory effects in human pancreas. Seventeen brain-dead patients and 20 control patients undergoing pancreatectomy were studied. Serum tumor necrosis factor (TNF), interleukin (IL) 6, IL-1β, interferon (IFN) γ, and TF were measured using enzyme-linked immunosorbent assay kits. Gene expressions of these cytokines and TF were evaluated by reverse transcriptase quantitative polymerase chain reaction. Protein quantification was performed by immunohistochemistry in paraffin-embedded pancreas sections., Results: Brain-dead patients had higher serum concentrations of TNF and IL-6 and increased TNF protein levels compared to controls. The groups had similar TNF, IL-6, IL-1β, and IFN-γ messenger RNA levels in pancreatic tissue. Reverse transcriptase quantitative polymerase chain reaction revealed TF messenger RNA up-regulation in controls. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls., Conclusions: Brain death induces inflammation evidenced by the up-regulation of TNF in serum 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.
- Published
- 2014
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