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

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Colleges, School and Institutes


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
Issue number3
Publication statusPublished - Sep 1989


  • 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