Tumour necrosis factor-alpha in murine autoimmune 'lupus' nephritis

Nature. 1988 Jan 28;331(6154):356-8. doi: 10.1038/331356a0.


The (NZB x NZW)F1 hybrid mouse develops a severe autoimmune disease similar to systemic lupus erythematosus in humans. Both the human and murine form of the disease show strong associations with alleles of the major histocompatibility complex (MHC) gene products. The severe form of the disease found in F1 mice is due, in part, to dominant NZW gene(s) mapping with the H-2 complex (the murine MHC). Here we present evidence that the tumour necrosis factor (TNF-alpha) gene, which is located within the H-2 complex (the murine major histocompatibility complex), could be involved in the pathogenesis of lupus nephritis in F1 mice. Thus, a restriction fragment length polymorphism in the TNF-alpha gene correlates with the reduced levels of TNF-alpha produced by NZW mice. Furthermore, replacement therapy with recombinant TNF-alpha induces a significant delay in the development of the nephritis.

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / metabolism
  • Female
  • Genes
  • Interferon-gamma / therapeutic use
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / genetics*
  • Lupus Nephritis / metabolism
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NZB
  • Polymorphism, Restriction Fragment Length
  • Tumor Necrosis Factor-alpha / deficiency*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / therapeutic use


  • Tumor Necrosis Factor-alpha
  • Interferon-gamma