CUX1 stimulates pancreatic cancer progression by modulating the NFκB-dependent cytokine expression in tumor-associated macrophages

s / Pancreatology Introduction: The endogenous immune response is influenced by vagotomy. Stimulation or destruction of the vagaus nerve leads to direct release of antior pro-inflammatorymediators. These mediators play a key role in the progression of mild edematous to severe necrotizing pancreatitis with systemic complications as pulmonary damage, SIRS and sepsis. The presented study analyzes the influence of pharmacologic stimulation of the vagal nerve system on the severity of experimental necrotizing pancreatitis in rats. Methods: A severe acute necrotizing pancreatitis was induced in rats by using the GDOC-model. Therapy groups received either nicotine, physiostigmin or neostigmin for stimulation of the vagal nerve system. The agents were applied either directly after induction of acute pancreatitis (prophylactic) or 3 hours in a delayed therapy group (therapeutic). The results were compared to animals that had pancreatitis alone or healthy controls. The evaluation was performed 12 hours after induction of acute necrotizing pancreatitis. Results: Histological evaluation of the pancreas in the pancreatitis only group confirmed a severe necrotizing pancreatitis compared to healthy controls regarding edema, inflammation and necrosis. Pharmacologic stimulation of the vagal nerve with nicotine, physiostigmin or neostigmin revealed an attenuated morphologic damage with regard to inflammation (p<0,005, respectively) and necrosis (p<0,05, respectively). The attenuated injury was independent of the application time (prophylactic or therapeutic). Conclusion: Pharmacologic stimulation of the vagal nerve attenuates pancreatic morphological injury in acute necrotizing pancreatitis in rats and should be further evaluated as a treatment approach.