Endotoxins and cytokines during liver transplantation: Changes in plasma levels and effects on clinical outcome

Endotoxins, tumor necrosis factor‐α (TNF‐α), interleukin‐1 (IL‐1), and IL‐6 are believed to have a key role in liver transplantation. The origin and course of these factors is not completely known. In this prospective study of 40 patients, we sought more understanding of the relations between these factors and their effects on clinical outcome by sampling at different sites. Endotoxemia was only present in 20% of the patients. In 75% of these patients, it was present during the anhepatic phase and quickly resolved after reperfusion. Endotoxemia was not related to a clinical adverse event. TNF‐α was released from the graft after reperfusion, and initial levels after reperfusion were related to predonation levels in the donor. Only levels of TNF‐α in the recipient before transplantation were found to be predictive of postoperative complications. We conclude that monitoring endotoxins and these cytokines is of very limited value in predicting outcome.

[1]  P. Boros,et al.  Differential contribution of graft and recipient to perioperative TNF-alpha, IL-1 beta, IL-6 and IL-8 levels and correlation with early graft function in clinical liver transplantation. , 1997, Clinical transplantation.

[2]  P. Neuhaus,et al.  Systemic liberation of interleukin-1β and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation , 1996, Transplant international : official journal of the European Society for Organ Transplantation.

[3]  S. Willatts,et al.  Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study. , 1996, Critical care medicine.

[4]  H. Sankary,et al.  Do splanchnic viscera contribute to liver preservation reperfusion injury? , 1996, Transplantation.

[5]  M. Haller,et al.  Perioperative mucosal pH and splanchnic endotoxin concentration in orthotopic liver transplantation. , 1996, British journal of anaesthesia.

[6]  S. Blanot,et al.  Circulating endotoxins and postreperfusion syndrome during orthotopic liver transplantation. , 1995, Transplantation.

[7]  D. Mathieu,et al.  The effects of donor and recipient endotoxemia on TNF alpha production and mortality in the rat model of syngenic orthotopic liver transplantation. , 1995, Transplantation.

[8]  M. Mittlböck,et al.  Tumour necrosis factor-alpha and interleukin-6: early indicators of bacterial infection after human orthotopic liver transplantation. , 1995, The European journal of surgery = Acta chirurgica.

[9]  P. Kragsbjerg,et al.  Serum concentrations of interleukin-6, tumour necrosis factor-alpha, and C-reactive protein in patients undergoing major operations. , 1995, The European journal of surgery = Acta chirurgica.

[10]  L. Moldawer,et al.  Assessment of the cytokine response in liver donors at the time of organ procurement and association with allograft function after orthotopic transplantation. , 1994, Journal of the American College of Surgeons.

[11]  E. Roth,et al.  TRANSHEPATIC METABOLISM OF TNF-α, IL‐6, AND ENDOTOXIN IN THE EARLY HEPATIC REPERFUSION PERIOD AFTER HUMAN LIVER TRANSPLANTATION , 1994, Transplantation.

[12]  G. Dedoussis,et al.  Abnormal cytokine serum levels correlate with impaired cellular immune responses after surgery. , 1994, Clinical immunology and immunopathology.

[13]  T. Ishiko,et al.  Elevation of circulating interleukin 6 after surgery: factors influencing the serum level. , 1994, Cytokine.

[14]  J. Bion,et al.  Selective decontamination of the digestive tract reduces Gram‐negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation , 1994, Critical care medicine.

[15]  J. Hurley,et al.  Endotoxin and tumor necrosis factor levels and hemodynamics during human liver transplantation. , 1993, Transplantation proceedings.

[16]  M. Stegall,et al.  Risk factors for primary dysfunction after liver transplantation--a multivariate analysis. , 1993, Transplantation.

[17]  J. Vincent,et al.  Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. , 1993, Chest.

[18]  L. W. Andersen,et al.  Association between gastric intramucosal pH and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor‐α concentrations in patients undergoing cardiopulmonary bypass , 1993, Critical care medicine.

[19]  E. Schiff,et al.  Activated cytokine pattern in hepatorenal syndrome: fall in levels after successful orthotopic liver transplantation. , 1993, Transplantation proceedings.

[20]  D. V. van Thiel,et al.  FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion. , 1993, Journal of hepatology.

[21]  H. Fusamoto,et al.  Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat , 1992, Hepatology.

[22]  H. Tilg,et al.  Serum levels of cytokines in chronic liver diseases. , 1992, Gastroenterology.

[23]  P. Clavien,et al.  Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. , 1992, Transplantation.

[24]  H. Büller,et al.  Effects on leukocytes after injection of tumor necrosis factor into healthy humans , 1992 .

[25]  A. Lienhart,et al.  Tumor necrosis factor-α in liver transplantation and resection: No evidence for a key role in ischemia-reperfusion injury , 1992 .

[26]  S. Hofbauer,et al.  Intraoperative course and prognostic significance of endotoxin, tumor necrosis factor-alpha and interleukin-6 in liver transplant recipients. , 1991, Immunobiology.

[27]  R. Steininger,et al.  Intraoperative estimation of endotoxin, TNF alpha, and IL-6 in orthotopic liver transplantation and their relation to rejection and postoperative infection. , 1991, Transplantation.

[28]  R. Auckenthaler,et al.  Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. , 1991, The American review of respiratory disease.

[29]  T. Starzl,et al.  EFFECT OF COLD ISCHEMIA TIME ON THE EARLY OUTCOME OF HUMAN HEPATIC ALLOGRAFTS PRESERVED WITH UW SOLUTION , 1991, Transplantation.

[30]  A. D. de Vos,et al.  Sensitive ELISA for interleukin-6. Detection of IL-6 in biological fluids: synovial fluids and sera. , 1991, Journal of immunological methods.

[31]  J. Lemasters,et al.  Kupffer cell activation and endothelial cell damage after storage of rat livers: Effects of reperfusion , 1991, Hepatology.

[32]  H. Büller,et al.  Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways , 1990 .

[33]  M. Salter,et al.  Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. , 1990, Biochemical and biophysical research communications.

[34]  R. Strieter,et al.  Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. , 1990, The Journal of clinical investigation.

[35]  T. Starzl,et al.  ENDOTOXAEMIA, PULMONARY COMPLICATIONS, AND THROMBOCYTOPENIA IN LIVER TRANSPLANTATION , 1989, The Lancet.

[36]  R. Pichlmayr,et al.  LIGNOCAINE METABOLITE FORMATION AS A MEASURE OF PRE-TRANSPLANT LIVER FUNCTION , 1989, The Lancet.

[37]  S. Heptinstall,et al.  RANDOMISED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL OF FEVERFEW IN MIGRAINE PREVENTION , 1988, The Lancet.

[38]  P. Nowell,et al.  Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. , 1988, The Journal of clinical investigation.

[39]  A. Waage Production and clearance of tumor necrosis factor in rats exposed to endotoxin and dexamethasone. , 1987, Clinical immunology and immunopathology.

[40]  J. Najarian,et al.  Liver Allograft Rejection : An Analysis of the Use of Biopsy in Determining Outcome of Rejection , 1987, The American journal of surgical pathology.

[41]  James Dg Letter: Dangerous Australian antigens. , 1975 .

[42]  T. Starzl,et al.  Experience in hepatic transplantation , 1969 .