Taurocholate-induced pancreatitis: a model of severe necrotizing pancreatitis in mice.
OBJECTIVE
The outcome from acute pancreatitis depends on the severity of systemic complications. To be able to investigate mechanisms underlying the development of these systemic complications in acute pancreatitis in both wild-type and genetically engineered animal models, a mouse model of severe necrotizing pancreatitis was developed and characterized.


METHODS
Pancreatitis was induced by retrograde infusion of sodium taurocholate into the common bile duct in mice. After determining the optimum volume and concentration of taurocholate, the pancreatic damage and systemic inflammatory response were compared with those in cerulein-induced pancreatitis.


RESULTS
Pancreatic damage was higher in taurocholate pancreatitis than hyperstimulation-induced pancreatitis (24 hours: cerulein, 5.8 +/- 0.2 points; taurocholate, 14.8 +/- 0.8 points; P < 0.001) and mortality reached up to 60% within the first 24 hours after taurocholate administration. Pulmonary damage was detected, as measured by an increase in albumin in bronchoalveolar lavage fluid only in taurocholate-induced pancreatitis (12 hours: cerulein, 97.1 +/- 22.83 mg/g of protein; taurocholate, 234.0 +/- 32.7 mg/g of protein; P < 0.001). Furthermore, plasma interleukin 6 concentration was significantly elevated in mice with taurocholate-induced pancreatitis (12 hours: cerulein, 2.6 +/- 6.1 pg/mL; taurocholate, 2168.8 +/- 941.7 microg/mL; P < 0.001) as compared with all other groups.


CONCLUSIONS
Taurocholate pancreatitis is a reliable model for severe necrotizing pancreatitis in mice with significantly greater pancreatic damage and systemic inflammatory response in comparison with cerulein-induced pancreatitis.
Wittel
Uwe A
UA
Department of General and Visceral Surgery, Universitätsklinik Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany. uwe.wittel@uniklinik-freiburg.de
Wiech
Thorsten
T
Chakraborty
Subhankar
S
Boss
Babette
B
Lauch
Robert
R
Batra
Surinder K
SK
Hopt
Ulrich T
UT
D000418:Albumins / Q000378:metabolism; D000681:Amylases / Q000097:blood; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002108:Ceruletide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007267:Injections; D015850:Interleukin-6 / Q000097:blood; D008049:Lipase / Q000097:blood; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000201:enzymology / Q000473:pathology*; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013656:Taurocholic Acid / Q000008:administration & dosage; D013997:Time Factors
D000418:Albumins; D015850:Interleukin-6; D013656:Taurocholic Acid; D002108:Ceruletide; D008049:Lipase; D000681:Amylases