Gordon C, Ranges G E, Greenspan J S, Wofsy D
Arthritis/Immunology Section, Veterans Administration Medical Center, San Francisco, California 94121.
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.
我们研究了重组鼠肿瘤坏死因子-α（TNF-α）对易患狼疮的NZB/NZW F1（B/W）小鼠自身免疫性疾病的影响。在临床疾病发作后开始用TNF-α治疗，与对照小鼠相比，其存活率有所提高：在10个月龄时，用TNF-α治疗的小鼠中有92%存活，而对照小鼠中这一比例为42%（P<0.05）。给予TNF-α可延缓肾脏疾病的进展，但持续治疗并不能防止严重肾炎的最终发展。尽管存活率有所提高，但用TNF-α治疗并未抑制抗双链DNA抗体的产生。然而，它加速了T淋巴细胞减少并消除了自然杀伤细胞活性。这些观察结果表明，TNF-α可能通过对细胞机制而非体液机制的影响来延缓B/W小鼠的狼疮病情。我们的研究结果还表明，TNF-α的有益作用不能通过长期治疗无限期维持。
