Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease

Hepatology. 2004 Oct;40(4):933-41. doi: 10.1002/hep.20400.


Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology including ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time. We therefore examined the effects of 10 days of interleukin 6 (IL-6) injection in 3 murine models of fatty liver: leptin deficient ob/ob mice, ethanol-fed mice, and mice fed a high-fat diet. In all 3 models, IL-6 injection decreased steatosis and normalized serum aminotransferase. The beneficial effects of IL-6 treatment in vivo resulted in part from an increase in mitochondrial beta oxidation of fatty acid and an increase in hepatic export of triglyceride and cholesterol. However, administration of IL-6 to isolated cultured steatotic hepatocytes failed to decrease lipid contents, suggesting that the beneficial effects of IL-6 in vivo do not result from its effects on hepatocytes alone. IL-6 treatment increased hepatic peroxisome proliferator-activated receptor (PPAR) alpha and decreased liver and serum tumor necrosis factor (TNF) alpha. Finally, 10 days of treatment with IL-6 prevented the susceptibility of fatty livers to warm ischemia/reperfusion injury. In conclusion, long-term IL-6 administration ameliorates fatty livers and protects against warm ischemia/reperfusion fatty liver injury, suggesting the therapeutic potential of IL-6 in treating human fatty liver disease.

MeSH terms

  • Animals
  • Cells, Cultured
  • Central Nervous System Depressants / pharmacology
  • DNA-Binding Proteins / metabolism
  • Dietary Fats / pharmacology
  • Down-Regulation
  • Ethanol / pharmacology
  • Fatty Liver / drug therapy*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver, Alcoholic / drug therapy
  • Fatty Liver, Alcoholic / metabolism
  • Gene Expression
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Interleukin-6 / pharmacology*
  • Male
  • Mice
  • Mice, Obese
  • Obesity / complications
  • Oxidation-Reduction
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • Central Nervous System Depressants
  • DNA-Binding Proteins
  • Dietary Fats
  • Interleukin-6
  • Receptors, Cytoplasmic and Nuclear
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Ethanol