Bacterial endotoxin: a trigger factor for alcoholic pancreatitis? Evidence from a novel, physiologically relevant animal model.

Abstract:

BACKGROUND & AIMS:This study examined the possible role of endotoxinemia (from increased gut permeability) as an additional trigger factor for overt pancreatic disease and as a promoter of chronic pancreatic injury in alcoholics by using a rat model of chronic alcohol feeding and in vitro experiments with cultured pancreatic stellate cells (PSCs), the key mediators of pancreatic fibrosis. METHODS:In the in vivo model, Sprague-Dawley rats fed isocaloric Lieber-DeCarli liquid diets +/- alcohol for 10 weeks were challenged with a single dose or 3 repeated doses of the endotoxin lipopolysaccharide (LPS) and the pancreas was examined. In the in vitro studies, rat PSCs were assessed for activation on exposure to LPS +/- ethanol. The expression of LPS receptors TLR4 and CD14 also was assessed in rat and human PSCs. RESULTS:In the in vivo model, single or repeated LPS challenge resulted in significantly greater pancreatic injury in alcohol-fed rats compared with rats fed the control diet without alcohol. Notably, repeated LPS injections caused pancreatic fibrosis in alcohol-fed rats, but not in rats fed the control diet. In the in vitro studies, PSCs were activated by LPS. Alcohol + LPS exerted a synergistic effect on PSC activation. Importantly, both rat and human PSCs expressed TLR4 and CD14. CONCLUSIONS:This study describes, for the first time, a clinically relevant animal model of alcohol-related pancreatic injury and provides strong in vivo and in vitro evidence that suggests that LPS is a trigger factor in the initiation and progression of alcoholic pancreatitis.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Vonlaufen A,Xu Z,Daniel B,Kumar RK,Pirola R,Wilson J,Apte MV

doi

10.1053/j.gastro.2007.06.062

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

1293-303

issue

4

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(07)01292-9

journal_volume

133

pub_type

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