Cited by 394Alcohol Consumption and Health EffectsLiver physiology and pathologyLiver Diseases and Immunity

The interleukin-17 pathway is involved in human alcoholic liver disease # †

Lemmers, Arnaud, Moreno, Christophe, Gustot, Thierry, Maréchal, Raphaël, Degré, Delphine, Demetter, Pieter, de Nadai, Patricia, Geerts, Albert +4 more·2009·Hepatology

Abstract

Immune dysregulations in alcoholic liver diseases are still unclear, especially regarding alcoholic hepatitis inflammatory burst. Interleukin-17 (IL-17) is known to enhance neutrophil recruitment. We studied the IL-17 pathway in alcoholic cirrhosis and alcoholic hepatitis. Patients with alcoholic liver disease were compared with patients with chronic hepatitis C virus (HCV) infection or autoimmune liver disease and with healthy controls. IL-17 plasma levels and peripheral blood mononuclear cell secretion were assessed by enzyme-linked immunosorbent assay (ELISA) and T cell phenotype by flow cytometry. IL-17 staining and co-staining with CD3 and myeloperoxidase were performed on liver biopsy specimens. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by chemotaxis assays. IL-17 plasma levels were dramatically increased in alcoholic liver disease patients. Peripheral blood mononuclear cells of patients with alcoholic liver disease produced higher amounts of IL-17, and their CD4 + T lymphocytes disclosed an IL-17–secreting phenotype. In the liver, IL-17–secreting cells contributed to inflammatory infiltrates in alcoholic cirrhosis, and alcoholic hepatitis foci disclosed many IL-17 + cells, including T lymphocytes and neutrophils. In alcoholic liver disease, liver IL-17 + cells infiltrates correlated to model for end-stage liver disease score, and in alcoholic hepatitis to modified discriminant function. IL-17 receptor was expressed in alcoholic liver disease by hepatic stellate cells, and these cells recruited neutrophils after IL-17 stimulation in a dose-dependent manner through IL-8 and growth related oncogen α (GRO-α) secretion in vitro . Conclusion: Human alcoholic liver disease is characterized by the activation of the IL-17 pathway. In alcoholic hepatitis, liver infiltration with IL-17–secreting cell infiltrates is a key feature that might contribute to liver neutrophil recruitment. (Clinical trials number NCT00610597). (Hepatology 2009;49:646–657.)

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Crossref · 10.1002/hep.22680

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  • IL-13 can induce and activate TGF-β in macrophages.

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    From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [133]

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Authors
Lemmers, A., Moreno, C., Gustot, T., Maréchal, R., Degré, D., Demetter, P., de Nadai, P., Geerts, A., Quertinmont, E., Vercruysse, V., Le Moine, O., & Devière, J.
Affiliations
  • Université Libre de Bruxelles (BE)
  • Vrije Universiteit Brussel (BE)
Corresponding author
Lemmers, Arnaud
Venue
Hepatology
Published
2009-02
Volume
49
Issue
2
Pages
646-657
ISSN
0270-9139 (ISSN-L)
OpenAlex
W2086396801
Cited by
394
References
57
Citations by year
2026: 7 · 2025: 14 · 2024: 21 · 2023: 18 · 2022: 15 · 2021: 17 · 2020: 23 · 2019: 20 · 2018: 23 · 2017: 26 · 2016: 16 · 2015: 35 · 2014: 30 · 2013: 37 · 2012: 32
FWCI
14.19
Type
journal article
Language
en
Open access
closed
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
IL-17, alcoholic liver disease, alcoholic hepatitis, alcoholic cirrhosis, neutrophil recruitment, IL-17 receptor, hepatic stellate cells, CD4+ T cells, liver inflammation, interleukin-8, CXCL1, Model for End-Stage Liver Disease, chronic hepatitis C, autoimmune liver disease
MeSH terms
Alanine Transaminase, Aspartate Aminotransferases, C-Reactive Protein, Female, Hepatitis, Alcoholic, Humans, Liver Cirrhosis, Liver Cirrhosis, Alcoholic, Male, Neutrophils, Reference Values, Hepatitis C, Chronic, Interleukin-17, Hepatic Stellate Cells

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