title: Elevated plasma levels of soluble tumor necrosis factor receptor (sTNFRp60) reflect severity of acute pancreatitis.
abstract: OBJECTIVE
  To investigate the role of activated leukocytes in acute pancreatitis, we measured soluble receptors of tumour necrosis factor alpha (sTNFR, p60 subtype) in plasma and evaluated the association of sTNFR with the clinical severity of the disease.
  
  
  METHODS
  Prospective, descriptive study.
  
  
  METHODS
  A medical intensive care unit (ICU) in a university hospital.
  
  
  METHODS
  25 consecutive ICU admissions of adult patients with acute pancreatitis.
  
  
  RESULTS
  The clinical severity of the disease was assessed using weights for the worst 17 physiological abnormalities of the Acute Physiology and Chronic Health Evaluation III score over a 24-h period after admission. According to the sum of these weights (giving the Acute Physiology Score, APS) patients were divided into a group with mild pancreatitis (APS < 25) and into a group with severe pancreatitis (APS > or = 25). Soluble TNFR was determined in plasma using an enzyme-linked immunoadsorbent assay. In patients with clinically severe pancreatitis, plasma sTNFR concentrations of 8.8 (16) ng/ ml (median, interquartile range) were significantly higher when compared to patients with mild disease [2.7 (1.5) ng/ml; p < 0.0001]. The sensitivity and specificity of sTNFR plasma concentrations (cutoff point at 5 ng/ml) for the prediction of severe pancreatitis were 90 and 100%, respectively. A highly positive correlation between sTNFR and deviations of physiological parameters from normal (APS score) was demonstrated (r = 0.81). The development of multiple organ failure (MOF) and death was associated with significantly higher sTNFR levels when compared to patients without MOF and survivors [16.4 (17) vs 3.2 (2) ng/ml, p = 0.0014 and 16.0 (18) vs 3.3 (4) ng/ml, p = 0.016, respectively]. For evidence of necrotizing pancreatitis, plasma C-reactive protein concentrations were measured and a significant exponential regression was found with sTNFR (r = 0.77, p < 0.0001). Patients developing pancreatic necrosis, as demonstrated by contrast-enhanced computed tomography, had significantly higher sTNFR concentrations when compared to patients with edematous pancreatitis [9.1 (17) vs 3.2 (2) ng/ml, p = 0.0018).
  
  
  CONCLUSIONS
  The p60 subtype of soluble TNFR is elevated in the plasma of patients with clinically severe acute pancreatitis. This elevation is positively correlated to abnormalities in physiological parameters, development of MOF, and mortality. The association with pancreatic necrosis suggests that, by mediating the effects of TNF, TNFRp60 reflects inflammatory tissue damage leading to severe systemic complications.
authors.affiliation: Department of Internal Medicine, Karl Franzens University, Graz, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Kaufmann
authors.forename: G P
authors.initials: GP
authors.lastname: Tilz
authors.forename: A
authors.initials: A
authors.lastname: Lueger
authors.forename: U
authors.initials: U
authors.lastname: Demel
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology; D010195:Pancreatitis / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D018124:Receptors, Tumor Necrosis Factor