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

C Gordon, G E Ranges, J S Greenspan, D Wofsy

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148 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)421-34
Number of pages14
JournalClinical immunology and immunopathology
Volume52
Issue number3
Publication statusPublished - Sep 1989

Keywords

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

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