Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Pancreatology 2009;9:258–266 DOI: 10.1159/000181176 Alcohol Pretreatment Increases Hepatic and Pulmonary Injury in Experimental Pancreatitis Lutz Schneider a Matthias Pietschmann a Werner Hartwig a Thilo Hackert a Sara S. Marcos a Thomas Longerich b Martha-Maria Gebhard c Markus W. Büchler a Jens Werner a Departments of a General Surgery, b Pathology, and c Experimental Surgery, University of Heidelberg, Heidelberg, Germany alcohol pretreatment, although they were also elevated in SNP alone. Systemic levels of IL-6 were higher than in the portal vein. Conclusion: In SNP, alcoholic pretreatment in- creases pulmonary damage, while pancreatic injury is identi- cal. The liver seems to participate in this effect by increased hepatic cytokine release. Copyright © 2009 S. Karger AG, Basel and IAP Introduction Severe necrotizing pancreatitis (SNP) occurs in ap- proximately 20% of all cases of acute pancreatitis and is still associated with high mortality rates of 10–40% [1]. Development of acute pancreatitis seems to follow simi- lar pathophysiological mechanisms regardless of the un- derlying etiology such as gallstones, alcohol, ischemia, and others [2]. Systemic complications such as pulmo- nary, renal, cardiovascular, or metabolic failure occur in about 50% of the patients with SNP. The high mortality of acute pancreatitis is mainly caused by multi-organ fail- ure or sepsis [3, 4] . Biliary and alcoholic pancreatitis rep- resent about 80% of all cases of SNP. Some authors sug- gest that alcoholic pancreatitis is more often associated with systemic complications than pancreatitis of other Key Words Kupffer cell  Pancreatitis, acute  Systemic complications  Lung injury Abstract Background: Systemic complications including pancreati- tis-associated lung injury (PALI) are critical factors that deter- mine the outcome of severe necrotizing pancreatitis (SNP). The aim of the present study was to evaluate the role of chronic alcohol exposure on the development of PALI. Meth- ods: 48 rats were fed either a Lieber deCarli control or alco- hol diet for 6 weeks. After completion, SNP was induced by intraductal infusion of bile salt followed by intravenous in- fusion of cerulein over 6 h. Control animals received i.v. Ring- er’s solution. Intravital microscopy of the liver was performed 6 h after induction of SNP to evaluate hepatic perfusion and leukocyte adhesion. Serum parameters, edema, inflamma- tion, and histological changes were evaluated at 12 h. IL-6 levels were evaluated in portal venous and systemic blood as well as in pancreatic tissue homogenates. Results: Alco- hol pretreatment did not affect pancreatic injury in SNP. PALI was aggravated after alcohol ingestion. These animals showed increased hepatic microcirculatory disturbances, compared to SNP alone. IL-6 showed peak levels in SNP with Received: April 8, 2008 Accepted after revision: October 29, 2008 Published online: April 29, 2009 Prof. Jens Werner, MD Department of Surgery, University of Heidelberg Im Neuenheimer Feld 110, DE–69120 Heidelberg (Germany) Tel. +49 6221 565 159, Fax +49 6221 565 969 E-Mail jens.werner@med.uni-heidelberg.de © 2009 S. Karger AG, Basel and IAP 1424–3903/09/0093–0258$26.00/0 Accessible online at: www.karger.com/pan