Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients

Authors

  • Alexander Khoruts,

    1. Department of Medicine, Minneapolis Veterans Administration Medical Center, Minneapolis, Minnesota 55417
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  • Laura Stahnke,

    1. Liver Research Core Center for the Study of Advanced Liver Disease, University of Minnesota, Minneapolis, Minnesota 55455
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  • Craig J. McClain,

    1. Division of Digestive Diseases and Nutrition, University of Kentucky College of Medicine, Lexington, Kentucky 40536
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  • George Logan,

    1. Saint Paul Ramsey Hospital, Saint Paul, Minnesota 55101
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  • John I. Allen

    Corresponding author
    1. Department of Medicine, Minneapolis Veterans Administration Medical Center, Minneapolis, Minnesota 55417
    2. Liver Research Core Center for the Study of Advanced Liver Disease, University of Minnesota, Minneapolis, Minnesota 55455
    • GI Section (111-D), VA Medical Center, One Veterans Dr., Minneapolis, MN 55417
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Abstract

Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-α, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-α and interleukin-1α concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-α and interleukin-1α are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury. (HEPATOLOGY 1991;13:267—276).

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