Immunologic Mechanisms of Alcoholic Liver Injury

Geoffrey M. Thiele; Thomas L. Freeman; Lynell W. Klassen

doi:10.1055/s-2004-832940

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2004; 24(3): 273-287
DOI: 10.1055/s-2004-832940

Immunologic Mechanisms of Alcoholic Liver Injury

Geoffrey M. Thiele¹ ^, ² , Thomas L. Freeman² , Lynell W. Klassen²

¹Professor, University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology and Immunology, Nebraska Medical Center and Department of Veterans Affairs Alcohol Research Center, Omaha Veterans Administration Medical Center, Omaha, Nebraska
²University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology and Immunology, Nebraska Medical Center and Department of Veterans Affairs Alcohol Research Center, Omaha Veterans Administration Medical Center, Omaha, Nebraska

Abstract

Clinically, the association of alcoholic liver disease (ALD) with circulating autoantibodies, hypergammaglobulinemia, antibodies to unique hepatic proteins, and cytotoxic lymphocytes reacting against autologous hepatocytes strongly suggests altered immune regulation with an increased activity toward normal self-proteins (loss of tolerance). Experimentally, there are several immune responses generated specifically recognizing self-proteins that are modified by metabolites of alcohol. These data strongly suggest that immune reactions may play a significant role in inducing and sustaining an inflammatory cascade of tissue damage to the liver. Additional support for this comes from the observation that the histological appearance of livers with ALD is that of a chronic active hepatitis-like inflammatory disease. Therefore, the hypothesis that immune mechanisms are involved in recurrent alcoholic hepatitis, although not summarily proven, is reasonable, supported by clinical and experimental evidence, and the subject of this article.

KEYWORDS

Antibodies - T cells - adducts - autoimmunity - immune responses

Full Text

References

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Geoffrey M ThielePh.D.

University of Nebraska Medical Center, Department of Internal Medicine, Section of Rheumatology and Immunology

983025 Nebraska Medical Center

Omaha, NE 68198-3025

Email: gthiele@unmc.edu