Elsevier

Alcohol

Volume 23, Issue 1, January 2001, Pages 29-34
Alcohol

Serum cytokine levels in alcohol-related liver cirrhosis

https://doi.org/10.1016/S0741-8329(00)00134-8Get rights and content

Abstract

Chronic alcoholism complicated by alcoholic liver disease is characterized by activation of the inflammatory response system. To evaluate the role of cytokines in the progress of alcoholic cirrhosis, we assessed serum level of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8 and the antiinflammatory cytokines IL-2, IL-10, and transforming growth factor (TGF)-β in patients with compensated and decompensated alcoholic liver cirrhosis. Compensated alcoholic cirrhosis was characterized by increased IL-6 (6.3±2.9 vs. HP 2.2±1.4 pg/ml in controls) and decreased IL-10 (HP 4.1±3.5 vs. 6.4±5.4 pg/ml in controls). TNF-α, IL-8, and TGF-β1 levels were comparable to those found in controls. In sera of patients with decompensated alcoholic liver cirrhosis, besides increased IL-6 (11.2±7.7 pg/ml), increased concentrations of TNF-α (25.1±4.5 vs. 9.1±7.0 pg/ml in controls) and IL-8 (171.7±294.0 vs. 2.7±2.9 pg/ml in controls) were also detected. TGF-β1 and IL-10 levels were similar to those found in controls. These results strongly indicate that a significant derangement of the balance between proinflammatory and antiinflammatory signals is characteristic of compensated and especially of decompensated alcoholic cirrhosis.

Introduction

Chronic alcoholism complicated by alcoholic liver disease (ALD) is characterized by activation of the inflammatory response system. Evidence of increased concentrations and activity of plasma cytokines produced by monocytes, macrophages, and hepatocytes, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-α (TNF-α) in patients with ALD, is now emerging. Increased cytokine activity correlates with the clinical course of liver disease and is of prognostic value. High levels of circulating TNF-α and IL-8 have been found to correlate with increased mortality in alcoholic hepatitis Bird et al., 1990, Felver et al., 1990, Hill et al., 1992, Khoruts et al., 1991, McClain et al., 1986, Sheron et al., 1991, Tilg et al., 1992. Although increased levels of several circulating cytokines in alcoholic liver cirrhosis have been reported Deviere et al., 1989, Deviere et al., 1991, Deviere et al., 1992, Hirsch et al., 1997, Huang et al., 1996, the association between cytokine levels and compensated and decompensated liver cirrhosis has not been examined.

To assess the role of cytokines in the development of alcoholic cirrhosis, we examined serum levels of the proinflammatory cytokines TNF-α, IL-6, and IL-8 and the antiinflammatory cytokines IL-2, IL-10, and also transforming growth factor (TGF)-β1 in patients with compensated and decompensated liver cirrhosis, expecting that imbalances in the relative levels of those groups of cytokines might reflect the clinical stage of alcoholic cirrhosis.

Section snippets

Patients

Patients with compensated (n=22) or decompensated (n=23) alcoholic liver cirrhosis were involved in this study. The mean age of patients with compensated and decompensated liver cirrhosis was 49 years. All patients had consumed at least 70 g of pure alcohol per day for more than 5 years. Most of the patients had consumed alcohol until a few days prior to admission to the hospital. However, upon exacerbation of disease, they ceased drinking, and none was acutely intoxicated at the time of entry

Results and discussion

In our study, we tried to find the cytokine pattern characteristic of compensated and decompensated alcoholic liver cirrhosis. As can be seen in Fig. 1, patients with compensated cirrhosis showed TNF-α, IL-8, and IL-2 levels comparable to those of controls; the IL-6 serum level alone was higher than that in controls. In contrast, patients with decompensated cirrhosis showed significantly higher levels of TNF-α, IL-6, IL-2, and IL-8 than did controls. The differences were statistically

References (29)

  • A. Castilla et al.

    Transforming growth factor β1 and α in chronic liver disease. Effects of interferon alpha therapy

    New Engl J Med

    (1991)
  • H.M. Dashti et al.

    Interleukin-8 and trace element alterations in experimentally induced liver cirrhosis: the influence of zinc, selenium, and allopurinol treatment

    J Trace Elem Exp Med

    (1996)
  • J. Deviere et al.

    Immunoglobulin A and IL-6 forms a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics

    Gastroenterology

    (1992)
  • J. Deviere et al.

    High interleukin-6 serum levels and increased production of by leukocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production

    Clin Exp Immunol

    (1989)
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