Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Herbert Tilg, Alexander R. Moschen, G. Szabó

Research output: Contribution to journalReview article

83 Citations (Scopus)

Abstract

Both alcoholic liver disease (ALD) and nonalcoholic fatty liver disease are characterized by massive lipid accumulation in the liver accompanied by inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma in a substantial subgroup of patients. At several stages in these diseases, mediators of the immune system, such as cytokines or inflammasomes, are crucially involved. In ALD, chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides through Toll-like receptors, e.g., Toll-like receptor 4. This sensitization enhances the production of various proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha, thereby contributing to hepatocyte dysfunction, necrosis, and apoptosis and the generation of extracellular matrix proteins leading to fibrosis/cirrhosis. Indeed, neutralization of IL-1 by IL-1 receptor antagonist has recently been shown to potently prevent liver injury in murine models of ALD. As IL-1 is clearly linked to key clinical symptoms of acute alcoholic hepatitis such as fever, neutrophilia, and wasting, interfering with the IL-1 pathway might be an attractive treatment strategy in the future. An important role for IL-1-type cytokines and certain inflammasomes has also been demonstrated in murine models of nonalcoholic fatty liver disease. IL-1-type cytokines can regulate hepatic steatosis; the NLR family pyrin domain containing 3 inflammasome is critically involved in metabolic dysregulation. Conclusion: IL-1 cytokine family members and various inflammasomes mediate different aspects of both ALD and nonalcoholic fatty liver disease. (Hepatology 2016;64:955-965).

Original languageEnglish
Pages (from-to)955-965
Number of pages11
JournalHepatology
Volume64
Issue number3
DOIs
Publication statusPublished - 2016

Fingerprint

Alcoholic Fatty Liver
Inflammasomes
Alcoholic Hepatitis
Alcoholic Liver Diseases
Interleukin-1
Cytokines
Fibrosis
Liver
Toll-Like Receptor 4
Kupffer Cells
Interleukin-1 Receptors
Extracellular Matrix Proteins
Toll-Like Receptors
Immune System Diseases
Gastroenterology
Non-alcoholic Fatty Liver Disease
Lipopolysaccharides
Hepatocytes
Hepatocellular Carcinoma
Fever

ASJC Scopus subject areas

  • Medicine(all)
  • Hepatology

Cite this

Interleukin-1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. / Tilg, Herbert; Moschen, Alexander R.; Szabó, G.

In: Hepatology, Vol. 64, No. 3, 2016, p. 955-965.

Research output: Contribution to journalReview article

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