Clinical Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 28, 2006; 12(40): 6507-6514
Published online Oct 28, 2006. doi: 10.3748/wjg.v12.i40.6507
Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis
Alexander Schneider, Stephan L Haas, Ralf Hildenbrand, Sören Siegmund, Iris Reinhard, Helmut Nakovics, Manfred V Singer, Peter Feick
Alexander Schneider, Stephan L Haas, Sören Siegmund, Manfred V Singer, Peter Feick, Department of Medicine II (Gastroenterology, Hepatology and Infectious Diseases), University Hospital of Heidelberg at Mannheim, Mannheim, Germany
Ralf Hildenbrand, Institute of Pathology University Hospital of Heidelberg at Mannheim, Mannheim, Germany
Iris Reinhard, Helmut Nakovics, Central Institute of Mental Health, Mannheim, Germany
Co-first-authors: Alexander Schneider and Stephan L Haas
Supported by a grant to MVS, Forschungsfonds, project number 098200/99-234, Faculty of Clinical Medicine, Uni-versity of Heidelberg at Mannheim, Germany; by a grant “Landesforschungsschwerpunkt-Molekulare Mechanismen alkoholassoziierter Erkrankungen”, project number 23-7532, Baden-Württemberg, Germany; and by the Dietmar-Hopp-Foundation, Walldorf, Germany
Correspondence to: Manfred V Singer, MD, Professor of Medicine and Chairman, Department of Medicine II (Gastroen-terology, Hepatology and Infectious Diseases), University Hospital of Heidelberg at Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim D-68135, Germany. manfred.v.singer@med.ma.uni-heidelberg.de
Telephone: +49-621-3833284 Fax: +49-621-3833805
Received: July 22, 2005
Revised: October 12, 2006
Accepted: November 10, 2006
Published online: October 28, 2006
Abstract

AIM: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP).

METHODS: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-γ and soluble CD14 in the serum were analysed by ELISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic IL-18 expression was performed.

RESULTS: In patients, IL-18 serum levels were significantly enhanced by 76% (mean: 289.9 ± 167.7 ng/L) compared with controls (mean: 165.2 ± 43.6 ng/L; P < 0.0005). IL-12 levels were enhanced by 25% in patients (18.3 ± 7.3 ng/L) compared with controls (14.7 ± 6.8 ng/L, P = 0.0576) although not reaching the statistical significance. IFN-γ and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dose-dependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas.

CONCLUSION: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.

Keywords: Chronic pancreatitis; Cytokines; Interleukin-18; Pancreatic fibrosis