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

Tumour necrosis factor (TNF) is a major mediator in septic shock and severa l 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 lipopolysac charide (LPS), interleukin-1 (IL-1) or TNF can desensitise against the leth ality 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 L iver Extract (MLE). The MLE desensitises; mice against the effects of TNF/G alN in a dose responsive way. The activity of the MLE is heat labile and do es 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 depend ent and heat labile and also possible in endotoxin-hyporesponsive C3H/HeJ m ice. The pure material protects against lethality, hypothermia and AST rele ase and it appears as a heat labile protein of relative molecular weight of 70 kDa probably with a break down product of 35 kDa. (C) 2001 Academic Pre ss.