Tatiana H Rech1, Daisy Crispim, Jakeline Rheinheimer, Sabrina S Barkan, Alessandro B Osvaldt, Tomaz J M Grezzana Filho, Cleber R P Kruel, Juliano Martini, Jorge L Gross, Cristiane B Leitão. 1. 1 Division of Intensive Care Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 2 Laboratory of Human Islet Biology, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 3 Division of Surgery, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 4 Address correspondence to: Tatiana Helena Rech, Ph.D., Division of Intensive Care Medicine of Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 13° andar, 90035-003, Porto Alegre-RS, Brazil.
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.
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.
Authors: R Oberhuber; P Ritschl; C Fabritius; A-V Nguyen; M Hermann; P Obrist; E R Werner; M Maglione; B Flörchinger; S Ebner; T Resch; J Pratschke; K Kotsch Journal: Am J Transplant Date: 2015-06-23 Impact factor: 8.086
Authors: Iestyn M Shapey; Angela Summers; Hussein Khambalia; Petros Yiannoullou; Catherine Fullwood; Neil A Hanley; Titus Augustine; Martin K Rutter; David van Dellen Journal: Diabetologia Date: 2021-03-04 Impact factor: 10.122
Authors: Juan S Danobeitia; Peter J Chlebeck; Inna Shokolenko; Xiaobo Ma; Glenn Wilson; Luis A Fernandez Journal: Cell Transplant Date: 2017-11 Impact factor: 4.064