title: Serum macrophage migration inhibitory factor is an early marker of pancreatic necrosis in acute pancreatitis.
abstract: OBJECTIVE
  To determine if 24-hour blood concentrations of macrophage migration inhibitory factor (MIF), soluble CD14, and CD163 receptors could predict complications associated with acute pancreatitis (AP).
  
  
  BACKGROUND
  Soluble receptor proteins derived from the macrophage-monocyte lineage potentiate the inflammatory cytokine response early in AP. Understanding the temporal expression of these molecules could afford better measures for therapeutic intervention.
  
  
  METHODS
  Patients with AP (amylase >5 times normal) were recruited within 24-hour of onset of pain. Peripheral blood was analyzed for MIF, sCD163, and sCD14 levels and levels correlated with CRP, APACHE-II score, and clinical disease severity (Atlanta criteria); subclassified as multiorgan dysfunction (MOF), pancreatic necrosis (PN >30% on contrast CT), and death.
  
  
  RESULTS
  In total, 64 patients with AP (severe, 19: 8 had MOF alone, 7 both PN and MOF, 2 PN without MOF, and 2 single-organ failures with local septic complications) were recruited. Both sCD14 and MIF concentrations were elevated in patients with severe attacks (P = 0.004 and P < 0.001 respectively), and patients who developed MOF (P = 0.004 and P < 0.001). However, only serum MIF was significantly raised in patients who subsequently developed PN (median, 92.5 ng/mL; IQR, 26-181 vs. 31.1 ng/mL; IQR, 5-82, P < 0.001), independently of MOF (P = 0.01). Multivariate analysis demonstrated serum MIF as an independent predictor of PN (P = 0.01; OR = 2.73; 95% CI, 2.72-2.74).
  
  
  CONCLUSIONS
  The prognostic utility of 24-hour plasma MIF concentration in predicting PN has major clinical and healthcare resource implications. Its mechanistic pathway may afford novel therapeutic interventions in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.
authors.affiliation: Division of Surgery, University of Leeds School of Medicine, St. James's University Hospital, UK. zak-rahman@lineone.net
authors.forename: Sakhawat H
authors.initials: SH
authors.lastname: Rahman
authors.forename: Krishna V
authors.initials: KV
authors.lastname: Menon
authors.forename: John H M
authors.initials: JH
authors.lastname: Holmfield
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McMahon
authors.forename: J Pierre
authors.initials: JP
authors.lastname: Guillou
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004739:England / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood* / Q000150:complications / Q000401:mortality; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood; D051116:Receptors, Scavenger / Q000097:blood; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D018950:Lipopolysaccharide Receptors; D008263:Macrophage Migration-Inhibitory Factors; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger