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A Role for Interleukin‐10 in Alcohol‐Induced Liver Sensitization to Bacterial Lipopolysaccharide
Author(s) -
Hill Daniell B.,
D'Souza Nympha B.,
Lee Eun Y.,
Burikhanov Ravshan,
Deaciuc Ion V.,
Villiers Willem J. S.
Publication year - 2002
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2002.tb02434.x
Subject(s) - proinflammatory cytokine , lipopolysaccharide , tumor necrosis factor alpha , liver injury , alcoholic liver disease , medicine , endocrinology , inflammation , cytokine , interleukin , steatosis , alanine transaminase , biology , immunology , cirrhosis
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.