Detection, characterisation and purification of a murine liver factor capable of desensitising towards the lethal activity of tumour necrosis factor

Cytokine. 2001 Jul 21;15(2):59-65. doi: 10.1006/cyto.2001.0912.


Tumour necrosis factor (TNF) is a major mediator in septic shock and several inflammatory diseases such as hepatitis. Galactosamine (GalN) sensitises experimental animals for TNF and the combination TNF/GalN leads to a lethal inflammatory hepatitis. We describe that a single injection of lipopolysaccharide (LPS), interleukin-1 (IL-1) or TNF can desensitise against the lethality induced by TNF/GalN, but also against changes in metabolic parameters such as hypothermia and transaminase release, in a dose responsive way. We also describe the desensitising capacity of a component present in Mouse Liver Extract (MLE). The MLE desensitises mice against the effects of TNF/GalN in a dose responsive way. The activity of the MLE is heat labile and does not involve LPS, TNF, IL-1 or TNF soluble receptors. We describe partial and complete purification of the factor. Partially pure material protects mice against all changes induced by TNF/GalN. The protection is dose dependent and heat labile and also possible in endotoxin-hyporesponsive C3H/HeJ mice. The pure material protects against lethality, hypothermia and AST release and it appears as a heat labile protein of relative molecular weight of 70 kDa probably with a break down product of 35 kDa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartate Aminotransferases / blood
  • Desensitization, Immunologic
  • Dose-Response Relationship, Drug
  • Female
  • Galactosamine / antagonists & inhibitors*
  • Galactosamine / immunology
  • Galactosamine / toxicity
  • Injections, Intraperitoneal
  • Interleukin-1 / administration & dosage*
  • Interleukin-1 / immunology
  • Lipopolysaccharides / administration & dosage*
  • Lipopolysaccharides / immunology
  • Liver / chemistry
  • Liver Extracts / chemistry
  • Liver Extracts / isolation & purification*
  • Liver Extracts / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Weight
  • Proteins / immunology
  • Proteins / isolation & purification
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / toxicity


  • Interleukin-1
  • Lipopolysaccharides
  • Liver Extracts
  • Proteins
  • Tumor Necrosis Factor-alpha
  • Galactosamine
  • Aspartate Aminotransferases