Recent understanding of immunological aspects in alcoholic hepatitis.
Alcoholic hepatitis is a rate-limiting step in the development of alcoholic liver disease into liver cirrhosis, and approximately half of the heavy drinkers with alcoholic hepatitis develop liver cirrhosis within 5 years. Immunologic mechanisms may be involved in the individual differences in the clinical course of this disease. Endotoxin from the intestine seems to play an important role in neutrophil infiltration of the liver, which induces, and at the same time is induced; by cytokines and chemokines. Kupffer cells and monocytes also have a key role in activating other cell types and producing several cytokines, chemokines, and free radicals. Both cytokines and chemokines up-regulate expression of various adhesion molecules, and adhesion molecules accelerate a cell-to-cell contact that stimulates cytotoxic lymphocytes to cause hepatocyte death. Self-antigens and adducts formed as a result of the degenerative effect of ethanol or aldehyde are targets of antibody-dependent cell-mediated cytotoxicity. Oxygen radicals, NF-kB, and AP-1 are key intracellular factors mediating hepatocyte death in alcoholic hepatitis. Viral infections and alcoholic hepatitis exacerbate each other. Integration of both human investigations and accumulated information from various animal models will gradually clarify the immunological mechanism of alcoholic hepatitis in future.
Saito
Hidetsugu
H
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Ishii
Hiromasa
H