Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice

Gastroenterology. 1996 Sep;111(3):736-44. doi: 10.1053/gast.1996.v111.pm8780580.


Background & aims: Tumor necrosis factor alpha (TNF-alpha) release plays a pivotal role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) administration in D-galactosamine (GalN)-sensitized mice. Interleukin (IL) 10 is an anti-inflammatory cytokine that inhibits TNF-alpha synthesis and release both in vitro and in vivo and prevents lethality from experimental endotoxemia. The present study was designed to ascertain whether in vivo treatment with IL-10 protects mice against LPS/GalN-induced liver injury.

Methods: Mice were treated with an intraperitoneal dose of LPS/GalN with or without IL-10 pretreatment. Liver injury was assessed biochemically and histologically, and plasma TNF-alpha levels, liver myeloperoxidase activity, and adhesion molecule expression were determined.

Results: Administration of LPS in GalN-sensitized mice caused lethal shock and massive hepatic necrosis in almost 100% of the mice. The effect was associated with a significant increase in plasma TNF-alpha concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens and circulating neutrophils. Pretreatment with IL-10 reduced plasma TNF-alpha concentrations and LPS/GalN-induced liver injury and lethality. Moreover, IL-10 reduced the LPS/GalN-induced liver neutrophil margination and up-regulation of adhesion molecules both on liver specimens and circulating neutrophils.

Conclusions: The present results suggest that IL-10 therapy could be useful in the treatment of TNF-alpha-mediated liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Chemical and Drug Induced Liver Injury*
  • Galactosamine / immunology*
  • Immunization*
  • Immunohistochemistry
  • Interleukin-10 / pharmacology*
  • Lipopolysaccharides* / poisoning
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Liver Diseases / mortality
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Peroxidase / metabolism
  • Tumor Necrosis Factor-alpha / analysis


  • Cell Adhesion Molecules
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Galactosamine
  • Peroxidase