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

被引:64
作者
Hashizume, Misato [1 ]
Uchiyama, Yasushi [1 ]
Horai, Naoto [2 ]
Tomosugi, Naohisa [3 ]
Mihara, Masahiko [1 ]
机构
[1] Chugai Pharmaceut Co Ltd, Prod Res Dept, Shizuoka 4128513, Japan
[2] Shin Nippon Biomed Labs Ltd, Drug Safety Res Labs, Kagoshima, Japan
[3] Kanazawa Med Univ, Med Res Inst, Div Adv Med, Kanazawa, Ishikawa, Japan
关键词
Tocilizumab; IL-6; Anemia; Collagen-induced arthritis; Hepcidin; COLLAGEN-INDUCED ARTHRITIS; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; CHRONIC DISEASE; DOUBLE-BLIND; TNF-ALPHA; IRON; INFLAMMATION; INTERLEUKIN-6; IL-6;
D O I
10.1007/s00296-009-1075-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:917 / 923
页数:7
相关论文
共 25 条
  • [21] Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial
    Smolen, Josef S.
    Beaulieu, Andre
    Rubbert-Roth, Andrea
    Ramos-Remus, Cesar
    Rovensky, Josef
    Alecock, Emma
    Woodworth, Thasia
    Alten, Rieke
    [J]. LANCET, 2008, 371 (9617) : 987 - 997
  • [22] TAKASHINA N, 1990, J RHEUMATOL, V17, P885
  • [23] Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System
    Tomosugi, Naohisa
    Kawabata, Hiroshi
    Wakatabe, Rumi
    Higuchi, Masato
    Yamaya, Hideki
    Umehara, Hisanori
    Ishikawa, Isao
    [J]. BLOOD, 2006, 108 (04) : 1381 - 1387
  • [24] Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorates joint swelling in established monkey collagen-induced arthritis
    Uchiyama, Yasushi
    Yorozu, Keigo
    Hashizume, Misato
    Moriya, Yoichiro
    Mihara, Masahiko
    [J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2008, 31 (06) : 1159 - 1163
  • [25] Anemia in monkey collagen-induced arthritis is correlated with serum IL-6, but not TNFα
    Uchiyama, Yasushi
    Koike, Nobuo
    Mihara, Masahiko
    [J]. RHEUMATOLOGY INTERNATIONAL, 2008, 28 (09) : 879 - 883