Endotoxin potentiates lung injury in cerulein-induced pancreatitis

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.