Supported by NIAAA Grants AA12314 (IVD), AA12774 (WJSDV), and AA00297 K24 (DBH). Also, this material is the result of work supported with resources and the use of facilities at the Lexington Veterans Administration Medical Center, Lexington, Kentucky.
A Role for Interleukin-10 in Alcohol-Induced Liver Sensitization to Bacterial Lipopolysaccharide
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 26, Issue 1, pages 74–82, January 2002
How to Cite
Hill, D. B., D'Souza, N. B., Lee, E. Y., Burikhanov, R., Deaciuc, I. V. and de Villiers, W. J. S. (2002), A Role for Interleukin-10 in Alcohol-Induced Liver Sensitization to Bacterial Lipopolysaccharide. Alcoholism: Clinical and Experimental Research, 26: 74–82. doi: 10.1111/j.1530-0277.2002.tb02434.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication April 27, 2001; accepted October 24, 2001.
- Proinflammatory Cytokines;
Background: Proinflammatory cytokines play an important role in alcohol-induced liver injury. The role of anti-inflammatory cytokines in the initiation and progression of alcoholic liver disease has received little attention. This study tested the hypothesis that an imbalance exists between pro- and anti-inflammatory cytokines in the liver during chronic exposure to alcohol. Alcohol exposure results in predominantly proinflammatory cytokine secretion and liver injury.
Methods: IL-10 knock-out and their C57BL/6J counterpart wild-type mice were fed alcohol in drinking water for 7 weeks. At the end of alcohol feeding, Gram-negative bacterial lipopolysaccharide (LPS) was administered, and the animals were killed after 3 and 8 hr. Liver histology, plasma alanine aminotransferase and aspartate aminotransferase activity, tumor necrosis factor-α, interleukin (IL)-1β and IL-10 levels, and liver cytokine messenger RNA levels were measured.
Results: Alcohol feeding and LPS treatment did not change plasma enzyme activity levels in wild-type mice. In the IL-10 knock-out mice, LPS alone increased aspartate aminotransferase and alanine aminotransferase enzyme activity, and this was potentiated by alcohol. Alcohol induced liver steatosis in both wild-type and knock-out mice. LPS markedly enhanced the histological effects further, especially in the knock-out mice, with the emergence of focal necrosis, polymorphonuclear infiltration, and microabscesses in the liver. Plasma tumor necrosis factor-α and IL-1β levels were not affected by alcohol alone. Proinflammatory cytokine levels were increased by LPS and further enhanced by alcohol treatment, particularly in the IL-10 knock-out mice. IL-10 plasma levels in the wild-type animals were down-regulated by alcohol. Changes in liver cytokine messenger RNA paralleled those seen in plasma cytokine levels.
Conclusions: Alcohol-induced liver sensitization to LPS in wild-type mice may involve down-regulation of IL-10. This anti-inflammatory cytokine, known for its hepatoprotective effects, is secreted simultaneously with proinflammatory cytokines. IL-10 may also limit alcohol-induced liver damage by counteracting the effects of proinflammatory cytokines.