A novel model of severe gallstone pancreatitis: Murine pancreatic duct ligation results in systemic inflammation and substantial mortality

Isaac Samuel, Zuobiao Yuan, David K. Meyerholz, Erik Twait, Deborah E. Williard, Duraisamy Kempuraj

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Suitable experimental models of gallstone pancreatitis with systemic inflammation and mortality are limited. We developed a novel murine model of duct-ligation-induced acute pancreatitis associated with multiorgan dysfunction and severe mortality. Methods: Laparotomy was done on C57/BL6 mice followed by pancreatic duct (PD) ligation, bile duct (BD) ligation without PD ligation, or sham operation. Results: Only mice with PD ligation developed acute pancreatitis and had 100% mortality. Pulmonary compliance was significantly reduced after PD ligation but not BD ligation. Bronchoalveolar lavage fluid neutrophil count and interleukin-1β concentration, and the plasma creatinine level, were significantly elevated with PD ligation but not BD ligation. Pancreatic nuclear factor κB (p65) and activator protein 1 (c-Jun) were activated within 1 h of PD ligation. Conclusion: PD-ligation-induced acute pancreatitis in mice is associated with systemic inflammation, acute lung injury, multiorgan dysfunction and death. The development of this novel model is an exciting and notable advance in the field.

Original languageEnglish (US)
Pages (from-to)536-544
Number of pages9
JournalPancreatology
Volume10
Issue number5
DOIs
StatePublished - Dec 2010

Keywords

  • Acinar cell
  • Acute lung injury
  • Acute pancreatitis
  • Cytokines
  • Mouse
  • Multiple-organ dysfunction syndrome
  • Nuclear factor κB
  • Systemic inflammatory response syndrome

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