Endotoxin potentiates lung injury in cerulein-induced pancreatitis

Keith D. Gray, Misho O. Simovic, William C. Chapman, Timothy S. Blackwell, John W. Christman, Addison K. May, Kelly S. Parman, Steven C. Stain

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Background: In this study we examine the effect of endotoxin (lipopolysaccharide) on lung injury in the setting of acute pancreatitis (AP). Methods: Twelve hourly injections of cerulein (50 μg/kg/h) were used to induce pancreatitis in mice. Intraperitoneal lipopolysaccharide (LPS [6 mg/kg]) was administered 24 hours after the initial cerulein injection. Twenty-four hours after LPS injection, myeloperoxidase (MPO) activity, nuclear factor (NF)-κB activation, and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and chemokines MIP-2 and KC levels were measured in pancreas, liver, and lung tissues. Four groups of mice were studied: cerulein-LPS, cerulein-saline, saline-LPS, and saline-saline treated mice. Results: Elevated serum lipase confirmed pancreatitis in cerulein treated mice. Lung MPO activity was significantly increased in the cerulein-LPS group. NF-κB was activated in the liver but not in pancreas and lung tissue. Chemokines MIP-2 and KC were elevated in pancreatic tissue only. Conclusions: These findings suggest that gram-negative infections may be an important predisposition for the development of adult respiratory distress syndrome in the setting of AP and that hepatic NF-κB may mediate multisystem injury.

Original languageEnglish
Pages (from-to)526-530
Number of pages5
JournalAmerican journal of surgery
Volume186
Issue number5
DOIs
StatePublished - Nov 2003

Keywords

  • Endotoxin
  • Lipopolysaccharide
  • Lung injury
  • Nuclear factor-κB
  • Pancreatitis

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