title: Anti-TNFalpha therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat.
abstract: BACKGROUND
  Elevated levels of tumor necrosis factor-alpha (TNFalpha) have been measured in a lethal model acute pancreatitis (AP) and may contribute to the pathophysiologic sequelae of the disease.
  
  
  METHODS
  To determine the significance of anti-TNFalpha therapy on survival and disease manifestations in a clinically relevant model of AP, a rat model was developed using a retrograde pancreatic ductal infusion of bile. Animals were randomized to no treatment (n = 30) or treatment with anti-TNFalpha antibody 15 minutes prior to induction of AP (n = 30). Five treated and 5 untreated rats were killed at various time periods up to 72 hours to provide temporal characterization of TNFalpha activity in AP.
  
  
  RESULTS
  A burst Of TNFalpha activity in the serum of untreated pancreatitis animals between 1 and 3 hours after induction of the disease is prevented by pretreatment with anti-TNFalpha antibody.
  
  
  CONCLUSIONS
  These findings provide a plausible mechanism for the improvement in biochemical and histologic parameters as well as in overall survival in an experimental model of acute pancreatitis in the rat.
authors.affiliation: Department of Surgery, University of Tennessee, College of Medicine, Memphis, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Hughes
authors.forename: H P
authors.initials: HP
authors.lastname: Grewal
authors.forename: L W
authors.initials: LW
authors.lastname: Gaber
authors.forename: M
authors.initials: M
authors.lastname: Kotb
authors.forename: A B
authors.initials: AB
authors.lastname: El-din
authors.forename: L
authors.initials: L
authors.lastname: Mann
authors.forename: A O
authors.initials: AO
authors.lastname: Gaber
mesh_terms: D000208:Acute Disease; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D014409:Tumor Necrosis Factor-alpha