title: Pharmacological cholinergic stimulation as a therapeutic tool in experimental necrotizing pancreatitis.
abstract: OBJECTIVE
  The endogenous immune response is influenced by the stimulation of the vagal nerve. Stimulation or ablation has a direct impact on the release of pro- and anti-inflammatory mediators. In the progression of acute pancreatitis from local to systemic disease, these mediators play a pivotal role. This study evaluates the effect of pharmacologic stimulation of the cholinergic system on pancreatic damage in experimental necrotizing pancreatitis.
  
  
  METHODS
  Experimental severe necrotizing pancreatitis was induced in male Wistar rats using the glycodeoxycholic acid model. Animals with acute pancreatitis (n = 6) were compared with animals with acute pancreatitis and prophylactic or therapeutic pharmacologic activation of the cholinergic system using nicotine, physostigmine, or neostigmine (n = 36). Twelve hours after the induction of acute pancreatitis, morphological damage as well as the myeloperoxidase levels of the pancreas and the serum levels of high-mobility group box 1 protein were evaluated.
  
  
  RESULTS
  Prophylactic and delayed therapeutic application of nicotine, physostigmine, or neostigmine significantly attenuated the severity of acute pancreatitis 12 hours after the induction of severe necrotizing pancreatitis compared with untreated controls as evaluated with histological scores, myeloperoxidase, and high-mobility group box 1 levels (P < 0.05).
  
  
  CONCLUSIONS
  Stimulation of the cholinergic system is useful to attenuate damage in experimental acute pancreatitis. Not only prophylactic but also delayed application was effective in the present study.
authors.affiliation: From the Departments of *General Surgery, and †Anesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schneider
authors.forename: Bahar
authors.initials: B
authors.lastname: Jabrailova
authors.forename: Hussein
authors.initials: H
authors.lastname: Soliman
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofer
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
mesh_terms: D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006002:Glycodeoxycholic Acid; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018678:Cholinergic Agents; D024243:HMGB1 Protein; D006002:Glycodeoxycholic Acid; D009388:Neostigmine; D009538:Nicotine; D010830:Physostigmine; D009195:Peroxidase