Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice

Clin Immunol Immunopathol. 1989 Sep;52(3):421-34. doi: 10.1016/0090-1229(89)90157-8.


We studied the effects of recombinant murine tumor necrosis factor-alpha (TNF-alpha) on autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Treatment with TNF-alpha, begun after the onset of clinical disease, improved survival relative to control mice: at age 10 months, 92% of mice treated with TNF-alpha were alive compared with 42% of control mice (P less than 0.05). Administration of TNF-alpha delayed the progression of renal disease, but sustained therapy did not prevent the eventual development of severe nephritis. Despite the improvement in survival, treatment with TNF-alpha did not inhibit anti-dsDNA antibody production. However, it accelerated T lymphocytopenia and abolished natural killer cell activity. These observations suggest that TNF-alpha may retard murine lupus in B/W mice through effects on cellular rather than humoral mechanisms. Our findings also indicate that the beneficial effects of TNF-alpha cannot be sustained indefinitely by chronic therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / analysis
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / therapy*
  • Blood Urea Nitrogen
  • DNA / immunology
  • Disease Models, Animal
  • Female
  • Immunotherapy
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Diseases / immunology
  • Kidney Diseases / pathology
  • Kidney Diseases / therapy
  • Killer Cells, Natural / immunology
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Erythematosus, Systemic / therapy*
  • Mice
  • Mice, Mutant Strains
  • Recombinant Proteins / therapeutic use
  • Tumor Necrosis Factor-alpha / therapeutic use*


  • Autoantibodies
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • DNA