Endotoxin potentiates lung injury in cerulein-induced pancreatitis

• Published in: The American journal of surgery 2003-11, Vol.186 (5), p.526-530
• Main Authors: Gray, Keith D, Simovic, Misho O, Chapman, William C, Blackwell, Timothy S, Christman, John W, May, Addison K, Parman, Kelly S, Stain, Steven C
• Format: Article
• Language: English
• Subjects: Animals; Bacterial infections; Biological and medical sciences; Ceruletide; Chemokines; Cytokines - metabolism; Endotoxin; Endotoxins - pharmacology; Enzymes; Gastroenterology. Liver. Pancreas. Abdomen; Injuries of the thorax. Foreign bodies. Diseases due to physical agents; Laboratory animals; Lipopolysaccharide; Liver - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung injury; Lungs; Male; Medical sciences; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; Nuclear factor-κB; Other diseases. Semiology; Pancreas; Pancreatitis; Pancreatitis - chemically induced; Peroxidase - metabolism; Potassium; Proteins; Respiratory distress syndrome; Respiratory Distress Syndrome, Adult - microbiology; Rodents; Traumas. Diseases due to physical agents
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2003.07.010

In this study we examine the effect of endotoxin (lipopolysaccharide) on lung injury in the setting of acute pancreatitis (AP). 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. 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. 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.