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Immunomodulation in a novel model of experimental chronic pancreatitis. | LitMetric

Immunomodulation in a novel model of experimental chronic pancreatitis.

Minerva Gastroenterol Dietol

Allgemein- und Visceralchirurgie, Stauferklinikum Schwäbisch Gmünd, Mutlangen, Germany.

Published: December 2012

AI Article Synopsis

  • - Chronic pancreatitis involves inflammation and damage to the pancreas, likely linked to the immune system, leading researchers to explore immune modulation as a potential treatment.
  • - In an experimental study on rats, researchers used the mTOR-inhibitor rapamycin (sirolimus) to observe its effect on pancreatitis over time, noting reduced damage and less chronic changes in treated animals.
  • - Results indicated that rats receiving sirolimus remained healthy and were normoglycemic, while placebo-treated rats developed diabetes, suggesting early immunomodulatory treatments could offer new options for managing chronic pancreatitis in humans.

Article Abstract

Chronic pancreatitis is a disease that involves the lymphocytic inflammation of the pancreatic gland, the destruction and fibrous transformation of the endocrine and ductal structures. An involvement of the immune system in the disease progression is assumed and possibly allows immune modulation as a novel treatment strategy. We used a new model of experimental chronic pancreatitis to examine the effect of immune modulation with the mTOR-inhibitor rapamycin on clinical, chemical and histological parameters of chronic pancreatitis. Pancreatitis was induced by injecting 8 mg/kg bodyweight DBTC intravenously in male Sprague Dawley rats. 24 and 72 hours later, 20 µg/kg bodyweight cerulein was injected intraperitoneally to simulate recurrent attacks of pancreatitis typical for the clinical course. 48 hours after the DBTC injection, rats were randomly allocated to placebo or sirolimus (1.5 mg/kg bw i.p.). The treatment was repeated every 24hours for 5 days. The rats were sacrificed 7, 14, 21 and 35 days after DBTC injection. Histologic examination revealed a reduced acute pancreatic damage in the treatment group in the first week and less chronic changes in the further course. ALT and amylase increased in Placebo animals over the observation period and was lower in sirolimus treated animals. Oral glucose tolerance test showed that all placebo animals were diabetic four weeks after DBTC while sirolimus treated animals were normoglycemic. An early, limited treatment with immunomodulatory and antifibrotic agents like sirolimus can positively influence the detrimental course of experimental chronic pancreatitis and may offer a treatment alternative in humans.

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