Gastroenterology

Gastroenterology

Volume 118, Issue 2, February 2000, Pages 356-367
Gastroenterology

Liver, Pancreas, and Biliary Tract
Differential expression of chemokines in normal pancreas and in chronic pancreatitis,☆☆

https://doi.org/10.1016/S0016-5085(00)70218-6Get rights and content

Abstract

Background & Aims: Cellular infiltrates are present already in early stages of chronic pancreatitis. The mechanisms responsible for their recruitment are unknown. Hence, we determined the differential expression of chemokine genes and their cellular sources in normal and affected pancreatic tissues. Methods: Pancreatic tissues from 23 patients with chronic pancreatitis and from 4 normal controls were subjected to in situ hybridization for detecting messenger RNA (mRNA) of the chemokine genes interleukin 8, ENA-78, MIG, MCP-1, and I-309. Results: Normal pancreatic tissues lack cells expressing mRNA for IL-8, ENA-78, MIG, and MCP-1. In contrast, pancreatic lobuli with mild to moderate signs of tissue alterations strongly expressed MCP-1 mRNA in centroacinar ducts, endothelia, fibroblasts, macrophages, T cells, and occasionally in nerves. Interleukin 8 and ENA-78 mRNA is preferentially detected in centroacinar ducts of pancreatic lobuli with more advanced alterations. Variable numbers of pancreas-infiltrating T cells express MIG mRNA. I-309 mRNA, however, is consistently observed in normal acini and in tissue with mild to moderate signs of tissue alterations. Conclusions: The observed differential expression of distinct chemokine genes in pancreatic parenchyma and infiltrates from patients with chronic pancreatitis strongly suggests an involvement of distinct chemokines in the initiation and perpetuation of disease.

GASTROENTEROLOGY 2000;118:356-367

Section snippets

Patients

Tissue specimens for the assessment of chemokine expression were obtained from 23 patients with CP. In most cases, CP was caused by a long history of excessive alcohol consumption; in 5 patients, the cause of CP was unidentified. None of the patients experienced an acute attack of pancreatitis in the 4-week period preceding surgical treatment, and all patients were reported to be abstinent from excessive alcohol consumption during this period. The patients did not receive any medicamentous

Histopathologic evaluation

All tissue specimens analyzed from patients with CP showed the histopathologic characteristics of CP with a heterogeneous pattern of extended fibrotic areas in vicinity to areas with remaining pancreatic parenchyma. Mononuclear cell infiltrates were observed on most tissue sections. Granulocytes were also present in low numbers on some sections; however, no other signs of acute inflammation were found, except for very rare, small foci of fat necrosis on 3 of 23 tissue specimens. Control

Discussion

Inflammatory infiltrates are frequently observed in the pancreas of patients with CP. Because the recruitment and activation of infiltrating cells are known to greatly depend on the local production of inflammatory mediators in inflamed tissues (reviewed by Rollins12), we attempted to assess whether production of chemokines could possibly contribute to the inflammatory response observed in CP.

Considering the large number of chemokines already identified, we decided to restrict our analysis to 5

Acknowledgements

The authors thank Dr. Robert Hunger for advice on the isolation of pancreas-infiltrating cells, Dr. Thomas Brunner for helpful discussions and critical reading of the manuscript, Maria Hodel for the careful preparation of the manuscript, and Marianne Bärtschi and Eliane Blank for preparation of the paraffin sections.

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  • Cited by (0)

    Supported by grants 31-43495.95 and 31-53961.98 from the Swiss National Science Foundation.

    ☆☆

    Address requests for reprints to: Christoph Mueller, Ph.D., Division of Immunopathology, Department of Pathology, University of Bern, Murtenstrasse 31, CH-3010 Bern/Switzerland. e-mail: [email protected]; fax: (41) 31-381-8764.

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