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 microg/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)-kappaB activation, and tumor necrosis factor (TNF)-alpha, 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-kappaB 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-kappaB may mediate multisystem injury.
Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Keith D
KD
Gray
Misho O
MO
Simovic
William C
WC
Chapman
Timothy S
TS
Blackwell
John W
JW
Christman
Addison K
AK
May
Kelly S
KS
Parman
Steven C
SC
Stain
D000818:Animals; D002108:Ceruletide; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced*; D009195:Peroxidase / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000382:microbiology*
D016207:Cytokines; D004731:Endotoxins; D016328:NF-kappa B; D002108:Ceruletide; D009195:Peroxidase