title: An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine model of acute hemorrhagic pancreatitis.
abstract: BACKGROUND
  Endothelin peptides are polykines with strong vasoconstrictor properties. We have previously shown that endothelin antagonism (PD145065) reduces the local severity of acute pancreatitis. We now investigated the effect of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic pancreatitis.
  
  
  METHODS
  Forty-two mice were divided into four groups. Group 1 was fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline-deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group 3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after initiation of diet. Animals were killed at 70 hours. Serum was collected. Pancreata and lung tissue were harvested.
  
  
  RESULTS
  Histology score, serum amylase level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were reduced in group 3 only (p < 0.05). The mortality rate did not differ among any of the groups.
  
  
  CONCLUSIONS
  Endothelin antagonism decreased the severity of acute pancreatitis and reduced markers of systemic inflammation. Late treatment at 48 hours failed to prevent the rise in IL-6. Mortality rates were unaffected by treatment.
authors.affiliation: Department of Surgery, Sepulveda VA Medical Center, Calif., USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Todd
authors.forename: M P
authors.initials: MP
authors.lastname: Lewis
authors.forename: B
authors.initials: B
authors.lastname: Gloor
authors.forename: J S
authors.initials: JS
authors.lastname: Lane
authors.forename: S W
authors.initials: SW
authors.lastname: Ashley
authors.forename: H A
authors.initials: HA
authors.lastname: Reber
mesh_terms: D000208:Acute Disease; D000818:Animals; D002796:Choline Deficiency; D016232:Endothelins / Q000037:antagonists & inhibitors*; D005001:Ethionine; D005260:Female; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D009842:Oligopeptides / Q000627:therapeutic use*; D010195:Pancreatitis / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016232:Endothelins; D009842:Oligopeptides; C082887:PD 145065; D005001:Ethionine