Goodfellow R M, Williams A S, Levin J L, Williams B D, Morgan B P
Department of Rheumatology, University of Wales College of Medicine, Cardiff, UK.
Clin Exp Immunol. 2000 Jan;119(1):210-6. doi: 10.1046/j.1365-2249.2000.01129.x.
We set out to determine whether inhibition of complement using sCR1 could influence the development and progression of collagen arthritis in the Lewis rat. Collagen arthritis was successfully established in the Lewis rat, using a novel immunization schedule. In separate experiments, cobra venom factor (CVF) and sCR1 were used to achieve systemic complement inhibition. Their respective effects on disease onset and on the progression of established disease compared with saline-treated control animals was explored. Arthritis was assessed by measurement of clinical score, paw diameter and paw volume. Complement inhibition using either CVF or sCR1, prior to the onset of clinical signs of inflammation, delayed the development of disease. CVF was ineffective in the treatment of established disease, whereas sCR1 delayed the progression of disease in affected joints and prevented the recruitment of further joints while the animals were complement-depleted. In the control saline-treated groups the disease continued to progress relentlessly. We conclude that complement activation is important in the initiation and maintenance of inflammation in collagen arthritis. The potent disease-modulating effect of sCR1 provides persuasive evidence that specific complement inhibiting agents may be an effective approach to the treatment of inflammatory joint diseases
我们着手研究使用可溶性补体受体1（sCR1）抑制补体是否会影响Lewis大鼠胶原性关节炎的发生和发展。采用一种新的免疫方案，在Lewis大鼠中成功诱导出胶原性关节炎。在单独的实验中，使用眼镜蛇毒因子（CVF）和sCR1来实现全身性补体抑制。探讨了它们与生理盐水处理的对照动物相比，对疾病发作和已确诊疾病进展的各自影响。通过测量临床评分、爪直径和爪体积来评估关节炎。在炎症临床症状出现之前，使用CVF或sCR1抑制补体可延迟疾病的发展。CVF对已确诊的疾病治疗无效，而sCR1可延迟患病关节疾病的进展，并在动物处于补体耗竭状态时防止更多关节受累。在生理盐水处理的对照组中，疾病持续无情进展。我们得出结论，补体激活在胶原性关节炎炎症的起始和维持中起重要作用。sCR1强大的疾病调节作用提供了有说服力的证据，表明特异性补体抑制剂可能是治疗炎性关节疾病的有效方法。
