Treatment of Crohn's disease with anti-IL-6 receptor antibody
Treatment of Crohn's disease with anti-IL-6 receptor antibody
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DOI：
10.1007/bf02990576
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发表时间：
2005-03-01
影响因子：
6.3
通讯作者：
Ito, H
中科院分区：
文献类型：
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作者：
Ito, H
我们通过使用T细胞转移小鼠结肠炎模型证明，用IL-6受体（IL-6R）单克隆抗体（mAb）阻断白细胞介素6 （IL-6）信号通路可消除固有层T细胞的凋亡抵抗，抑制血管粘附分子的表达，成功预防和治疗肠道炎症。基于这些结果，我们开展了一项探索性临床试验，以研究人源化抗il - 6r单抗（MRA）治疗克罗恩病（CD）患者的安全性和有效性。结果很有希望，80%的患者每2周注射一次MRA，持续12周，与安慰剂治疗患者的31%相比，临床反应率显着提高。该方案中20%的患者进入缓解期，而安慰剂组为0%。急性期反应通过单次MRA输注正常化，这强烈表明IL-6是CD中负责其产生的主要细胞因子。
We have demonstrated, by using a T-cell transfer murine colitis model, that blocking interleukin 6 (IL-6) signaling with monoclonal antibody (mAb) to IL-6 receptor (IL-6R) abrogated apoptosis resistance of lamina propria T cells, suppressed the expression of vascular adhesion molecules, and successfully prevented and treated intestinal inflammation. Based on these results, we carried out an exploratory clinical trial to investigate the safety and efficacy of humanized anti-IL-6R mAb, MRA, in patients with Crohn's disease (CD). The results were promising, with 80% of the patients given every-2-week MRA infusions for 12 weeks showing a significantly higher clinical response rate as compared to 31% of the placebo-treated patients. Twenty percent of the patients on this regimen went into remission as compared to 0% of the placebo group. The acute-phase responses were normalized by a single MRA infusion, which strongly suggests IL-6 is the major cytokine responsible for their production in CD.