Atzeni Fabiola, Doria Andrea, Carrabba Mario, Turiel Maurizio, Sarzi-Puttini Piercarlo
Rheumatology Unit, L. Sacco Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
Autoimmun Rev. 2007 Sep;6(8):529-36. doi: 10.1016/j.autrev.2007.03.009. Epub 2007 Apr 16.
Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by many cell types (blood monocytes, macrophages, mast cells and endothelial cells), that play a key role in the pathogenesis of multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well tolerated in patients with Crohn's disease, rheumatoid arthritis and spondiloarthritides and has become a widely used treatment for these diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists: Behçet's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis have been shown to improve with infliximab. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjögren's syndrome as evidenced by the lack of efficacy of TNF antagonists. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. A number of other more rare disorders also may be responsive to TNF blockade. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions.
肿瘤坏死因子-α(TNF-α)是一种由多种细胞类型(血液单核细胞、巨噬细胞、肥大细胞和内皮细胞)产生的促炎细胞因子,在多种自身免疫性和非自身免疫性疾病的发病机制中起关键作用。多项大型安慰剂对照试验表明,英夫利昔单抗,一种抗TNF-α的嵌合单克隆抗体,在克罗恩病、类风湿关节炎和脊柱关节炎患者中有效且耐受性良好,已成为这些疾病广泛使用的治疗方法。初步数据表明,几种血管炎形式似乎对TNF拮抗剂有反应:白塞病、变应性肉芽肿性血管炎、结节性多动脉炎和巨细胞动脉炎等。韦格纳肉芽肿病和结节病已显示使用英夫利昔单抗后病情改善。多发性肌炎/皮肌炎可能也对TNF阻断有反应。TNF在干燥综合征中可能作用不大,这由TNF拮抗剂缺乏疗效证明。即使在系统性红斑狼疮(一种自身抗体介导疾病的原型)中使用TNF阻断也有理论依据,一项初步研究似乎证实了这种潜在有效的方法。许多其他更罕见的疾病也可能对TNF阻断有反应。我们在此综述英夫利昔单抗在自身免疫性疾病和其他病症治疗中的当前及未来作用。