title: Assessment of the cytokine response in liver donors at the time of organ procurement and association with allograft function after orthotopic transplantation.
abstract: BACKGROUND
  The cause of allograft liver dysfunction after transplantation is unresolved. We tested the hypothesis that human donor liver may be predisposed to ischemia reperfusion injury, and graft dysfunction subsequent to ongoing inflammatory processes during donor hospitalization.
  
  
  METHODS
  A prospective study of organ donors and transplant recipients of allograft livers from these donors was conducted. Portal venous, inferior vena caval, and superior vena caval blood samples were obtained from 16 clinical organ donors at the time of organ procurement (one to 12 days post-trauma) to characterize the hepatic cytokine and acute phase protein response, to determine whether or not this response resulted from bacterial or endotoxin translocation to the portal circulation, and to assess whether or not transplant outcome was associated with plasma levels of cytokines in the donor.
  
  
  RESULTS
  In comparison with systemic blood samples from ten healthy persons, all 16 donors exhibited significantly (p < 0.05) elevated plasma concentrations of interleukin-6, interleukin-8, soluble p55 tumor necrosis factor receptor type I (sTNFr-I), and C-reactive protein. No concentration differences existed among portal venous, inferior vena caval, and superior vena caval blood samples for any cytokine or acute phase protein measured. Donor levels of endotoxin, TNF-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), alpha 1-acid glycoprotein, alpha 1-antitrypsin, and haptoglobin were comparable with those in the healthy persons. Bacterial cultures of portal blood were negative. There was no association between the causation of donor trauma and either donor cytokine response or function and quality of the allograft liver after transplantation. Nor could an association between donor cytokine response and either early allograft function (less than 96 hours) or eventual transplant outcome in the recipients be detected.
  
  
  CONCLUSIONS
  These results indicate that, although an ongoing inflammatory response to injury was evident in these donors at the time of organ procurement, there were no apparent adverse effects arising from these inflammatory processes on the function and quality of the donor liver after transplantation. Bacterial translocation does not seem to be a component of the pathogenesis of inflammation. Whether or not the presence of inflammation in the donor alters the metabolic responses of the allograft liver and recipient to transplant operation is unknown.
authors.affiliation: Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston 02215.
authors.forename: J D
authors.initials: JD
authors.lastname: Palombo
authors.forename: P A
authors.initials: PA
authors.lastname: Burke
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: R A
authors.initials: RA
authors.lastname: Forse
authors.forename: W D
authors.initials: WD
authors.lastname: Lewis
authors.forename: R L
authors.initials: RL
authors.lastname: Jenkins
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D016470:Bacteremia / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000097:blood; D005260:Female; D006085:Graft Survival; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011168:Portal System; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D014019:Tissue Donors; D014021:Tissue Preservation; D009927:Tissue and Organ Procurement; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000209:Acute-Phase Proteins; D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein