title: Inflammatory profiling of early experimental necrotizing pancreatitis.
abstract: OBJECTIVE
  Inflammatory mediators play a pivotal role in severe necrotizing pancreatitis (SNP). Therapeutic approaches aim at the early inflammatory liberation of cytokines to avoid systemic complications. The present study evaluates the kinetics of inflammatory mediator release in SNP.
  
  
  METHODS
  Experimental SNP was induced in male Wistar rats using the GDOC model. The animals were allocated into seven groups (n = 6/group). In group 1, sample harvesting was performed after sham operation while in groups 2-7 this was performed 1 h, 2 h, 4 h, 6 h, 9 h, and 12 h after initiation of SNP, respectively. Inflammatory mediator release,morphologic injury, and tissue MPO concentrations were evaluated between 1 and 12 h after induction.
  
  
  RESULTS
  Pancreatic injury showed a continuous increase over the observation period (p b 0.05, respectively). MPO levels in the pancreas and lungs increased until 12 h after induction (p b 0.05, respectively). Antiinflammatory IL-10 showed an early peak and the pro-inflammatory mediators TNFα and IL-1β peaked after 6 and 9 h, respectively (p b 0.05, respectively). HMGB1 levels constantly increased over time (p b 0.05, respectively).
  
  
  CONCLUSIONS
  The present study shows the release of relevant pro- and anti-inflammatory mediators in SNP for the first time in one single experimental setup. Inflammatory mediators peak within the first few hours after SNP induction. Consequently, the effect of therapeutic approaches on early changes in cytokine release should be evaluated later than 2 h after initiation.
authors.affiliation: Department for General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address: Lutz.Schneider@med.uni-heidelberg.de.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schneider
authors.affiliation: Department for General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Bahar
authors.initials: B
authors.lastname: Jabrailova
authors.affiliation: Department for General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.affiliation: Department for General, Visceral, and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.affiliation: Department for General, Visceral, Transplantation, Thoracic, and Vascular Surgery, University of Munich, Nußbaumstraße 20, 80336 Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: Acute pancreatitis; Cytokines; Experimental; Myeloperoxidase; Necrotizing pancreatitis; Severe pancreatitis; Systemic complications