title: Brain death-induced inflammatory activity in human pancreatic tissue: a case-control study.
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.
authors.affiliation: 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.
authors.forename: Tatiana H
authors.initials: TH
authors.lastname: Rech
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
authors.forename: Jakeline
authors.initials: J
authors.lastname: Rheinheimer
authors.forename: Sabrina S
authors.initials: SS
authors.lastname: Barkan
authors.forename: Alessandro B
authors.initials: AB
authors.lastname: Osvaldt
authors.forename: Tomaz J M
authors.initials: TJ
authors.lastname: Grezzana Filho
authors.forename: Cleber R P
authors.initials: CR
authors.lastname: Kruel
authors.forename: Juliano
authors.initials: J
authors.lastname: Martini
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gross
authors.forename: Cristiane B
authors.initials: CB
authors.lastname: Leitão
mesh_terms: D000328:Adult; D000368:Aged; D001926:Brain Death / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology*; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma