| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Medicine,* Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania; the Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania; the Veteran’s Administration Health System of Pittsburgh, Pittsburgh, Pennsylvania
Alcohol consumption is a risk factor for chronic pancreatitis (CP), but the mechanism in humans remains obscure because prolonged alcohol consumption in most humans and animal models fails to produce alcoholic chronic pancreatitis (ACP). We hypothesize that the process leading to ACP is triggered by a sentinel acute pancreatitis (AP) event; this event causes recruitment of inflammatory cells, which initiates fibrosis driven by the anti-inflammatory response to recurrent AP and/or chronic oxidative stress. The aim was to determine whether chronic alcohol consumption accelerates fibrosis in response to cerulein-induced pancreatitis in the rat. Wistar male rats were pair-fed control (C) or 5% ethanol (E) Lieber-DeCarli liquid diets. Animals were studied without pancreatitis (P0), with cerulein pancreatitis induced once (P1), or with cerulein-induced pancreatitis weekly for 3 weeks (P3). AP markers, inflammation, and fibrosis were measured histologically, by gene expression profiling and protein expression. Macrophage infiltration was reduced in EP0 versus CP0 rats, but the pattern was reversed after AP. Microabscess, severe necrosis, and early calcification were only induced in the EP3 rats. Fibrosis was significantly induced in the EP3 rats versus EP1, CP1, and CP3 by histology, hydroxyproline content, and mRNA expression for collagen 
1(1) and procollagen 2(1). Proinflammatory cytokine mRNAs were up-regulated shortly after induction of AP, while the anti-inflammatory cytokines (interleukin-10 and transforming growth factor-ß) were strongly up-regulated later and in parallel with fibrogenesis, especially in the EP3 rats. Pancreatic fibrosis develops after repeated episodes of AP and is potentiated by alcohol. Expression of fibrosis-associated genes was associated with expression of anti-inflammatory cytokines in alcohol-fed rats.
This article has been cited by other articles:
 |
|
 |
|
  D. Yadav, R. H. Hawes, R. E. Brand, M. A. Anderson, M. E. Money, P. A. Banks, M. D. Bishop, J. Baillie, S. Sherman, J. DiSario, et al. Alcohol Consumption, Cigarette Smoking, and the Risk of Recurrent Acute and Chronic Pancreatitis Arch Intern Med, June 8, 2009; 169(11): 1035 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gukovsky, A. Lugea, M. Shahsahebi, J. H. Cheng, P. P. Hong, Y. J. Jung, Q.-g. Deng, B. A. French, W. Lungo, S. W. French, et al. A rat model reproducing key pathological responses of alcoholic chronic pancreatitis Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G68 - G79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Fortunato, X. Deng, L. K. Gates, C. J. McClain, D. Bimmler, R. Graf, and D. C. Whitcomb Pancreatic response to endotoxin after chronic alcohol exposure: switch from apoptosis to necrosis? Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G232 - G241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Perides, X Tao, N West, A Sharma, and M L Steer A mouse model of ethanol dependent pancreatic fibrosis Gut, October 1, 2005; 54(10): 1461 - 1467. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
