Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production
Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production
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DOI：
10.1007/s00296-009-1075-4
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发表时间：
2010-05-01
影响因子：
4
通讯作者：
Mihara, Masahiko
中科院分区：
文献类型：
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作者：
Hashizume, Misato;Uchiyama, Yasushi;Mihara, Masahiko
我们已有报道，在胶原性关节炎(CIA)模型中，血清IL-6水平与贫血程度有关。在这项研究中，我们研究了IL-6阻断是否能改善猴子CIA的贫血。用佐剂二次免疫牛II型胶原诱导CIA。当贫血明显时，抗IL-6受体抗体tocilizumab每周静脉注射一次，连续4周。控制组以同样的方式收到PBS。定期检测血液学和生化指标，用SELDI-TOF质谱仪测定血清海普西丁-25水平。同时，用实时荧光定量聚合酶链式反应检测了关节炎猴血清对Hep3B细胞中海普西丁的诱导作用。托西珠单抗在1周内迅速降低CRP水平并改善缺铁性贫血。Tocilizumab可引起血清中海普西丁-25的快速但短暂的下降。关节炎猴血清可更有效地诱导海普西丁mRNA的表达，而tocilizumab可抑制其表达。阻断IL-6信号，通过抑制IL-6诱导的海普西丁的产生，迅速改善猴子关节炎的贫血。
We have reported that serum IL-6 level was related with the degree of anemia in monkey collagen-induced arthritis (CIA). In this study, we examined whether IL-6 blockade ameliorated an anemia in monkey CIA. CIA was induced by twice immunization of bovine type II collagen with adjuvant. When anemia became evident, anti-IL-6 receptor antibody, tocilizumab was intravenously injected once a week for 4 weeks. Controls received PBS in a same manner. Hematological and biochemical parameters were measured regularly and serum hepcidin-25 levels were measured by SELDI-TOF mass spectrometry. Moreover, hepcidin mRNA induction in Hep3B cells by serum from arthritic monkeys was examined by real-time PCR. Administration of tocilizumab rapidly decreased CRP levels and improved iron-deficient anemia within 1 week. Tocilizumab induced rapid but transient reduction in serum hepcidin-25. Hepcidin mRNA expression was more potently induced by serum from arthritic monkey and this was inhibited by the addition of tocilizumab. Blockade of IL-6 signaling rapidly improved anemia in monkey arthritis via the inhibition of IL-6-induced hepcidin production.