HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 294/1/G68    most recent 00006.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gukovsky, I. Articles by Pandol., S. J. Search for Related Content PubMed PubMed Citation Articles by Gukovsky, I. Articles by Pandol., S. J.

INFLAMMATION/IMMUNITY/MEDIATORS

A rat model reproducing key pathological responses of alcoholic chronic pancreatitis

¹Veterans Affairs Greater Los Angeles Healthcare System, ²USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, ³University of California at Los Angeles, and ⁴Harbor-UCLA Medical Center, Torrance, California

Submitted 5 January 2007 ; accepted in final form 19 September 2007

Although alcohol abuse is the major cause of chronic pancreatitis, the pathogenesis of alcoholic chronic pancreatitis (ACP) remains obscure. A critical obstacle to understanding the mechanism of ACP is lack of animal models. Our objective was to develop one such model. Rats were pair-fed for 8 wk ethanol or control Lieber-DeCarli liquid diet. For the last 2 wk, they received cyclosporin A (CsA; 20 mg/kg once daily) or vehicle. After 1 wk on CsA, one episode of acute pancreatitis was induced by four 20 µg/kg injections of cerulein (Cer); controls received saline. Pancreas was analyzed 1 wk after the acute pancreatitis. CsA or Cer treatments alone did not result in pancreatic injury in either control (C)- or ethanol (E)-fed rats. We found, however, that alcohol dramatically aggravated pathological effect of the combined CsA+Cer treatment on pancreas, resulting in massive loss of acinar cells, persistent inflammatory infiltration, and fibrosis. Macrophages were prominent in the inflammatory infiltrate. Compared with control-fed C+CsA+Cer rats, their ethanol-fed E+CsA+Cer counterparts showed marked increases in pancreatic NF-B activation and cytokine/chemokine mRNA expression, collagen and fibronectin, the expression and activities of matrix metalloproteinase-2 and -9, and activation of pancreatic stellate cells. Thus we have developed a model of alcohol-mediated postacute pancreatitis that reproduces three key responses of human ACP: loss of parenchyma, sustained inflammation, and fibrosis. The results indicate that alcohol impairs recovery from acute pancreatitis, suggesting a mechanism by which alcohol sensitizes pancreas to chronic injury.

ethanol; inflammatory response; pancreatic stellate cells; cerulein; cyclosporin A

This article has been cited by other articles:

				L. Jiao, D. T. Silverman, C. Schairer, A. C. M. Thiebaut, A. R. Hollenbeck, M. F. Leitzmann, A. Schatzkin, and R. Z. Stolzenberg-Solomon Alcohol Use and Risk of Pancreatic Cancer: The NIH-AARP Diet and Health Study Am. J. Epidemiol., May 1, 2009; 169(9): 1043 - 1051. [Abstract] [Full Text] [PDF]