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Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production

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Abstract

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.

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Authors and Affiliations

  1. Product Research Department, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan

    Misato Hashizume, Yasushi Uchiyama & Masahiko Mihara

  2. Drug Safety Research Labs, Shin Nippon Biomedical Laboratories, Ltd, Kagoshima, Japan

    Naoto Horai

  3. Division of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan

    Naohisa Tomosugi

Authors
  1. Misato Hashizume
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  2. Yasushi Uchiyama
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  3. Naoto Horai
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  4. Naohisa Tomosugi
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  5. Masahiko Mihara
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Correspondence to Masahiko Mihara.

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Hashizume, M., Uchiyama, Y., Horai, N. et al. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production. Rheumatol Int 30, 917–923 (2010). https://doi.org/10.1007/s00296-009-1075-4

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  • DOI: https://doi.org/10.1007/s00296-009-1075-4

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