The isolated perfused liver response to a 'second hit' of portal endotoxin during severe acute pancreatitis.
OBJECTIVE
During severe acute pancreatitis (AP), the liver may show an exaggerated response to the inflammatory products of gut injury transported in the portal vein. Our aim was to explore liver proinflammatory mediator production after a 'second hit' of portal lipopolysaccharide (LPS) during AP.


METHODS
Twenty-four rats underwent one of three 'first-hit' scenarios: (1) severe AP induced by intraductal glycodeoxycholic acid injection and intravenous caerulein infusion, (2) sham laparotomy, or (3) no first intervention. Eighteen hours later, all animals received a 'second hit' of portal LPS in an isolated liver perfusion system. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 concentrations were measured in portal and systemic serum, and in the perfusate 30 and 90 min after the 'second hit'. Neutrophil activation by the perfusate was assayed using dihydrorhodamine-123 fluorescence.


RESULTS
We observed a six-fold increase in IL-6 concentration across the liver during AP. All livers produced TNF-alpha after the portal LPS challenge, but this was not exaggerated by AP. No differential neutrophil activation by the perfusate was seen.


CONCLUSIONS
TNF-alpha, IL-1beta, IL-6 and neutrophil activator production by the isolated perfused liver, in response to a 'second hit' of portal LPS, does not appear to be enhanced during AP.
Department of Surgery, Queen's University of Belfast, Belfast, Northern Ireland. damianmole@ntlworld.com
Damian J
DJ
Mole
Mark A
MA
Taylor
Neil V
NV
McFerran
Thomas
T
Diamond
D000681:Amylases / Q000097:blood; D000818:Animals; D021461:Animals, Outbred Strains; D002108:Ceruletide / Q000494:pharmacology; D004195:Disease Models, Animal; D006002:Glycodeoxycholic Acid / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D016897:Respiratory Burst / Q000187:drug effects; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D006002:Glycodeoxycholic Acid; D002108:Ceruletide; D000681:Amylases