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

M Hashizume, Y Uchiyama, N Horai… - Rheumatology …, 2010 - Springer
M Hashizume, Y Uchiyama, N Horai, N Tomosugi, M Mihara
Rheumatology international, 2010Springer
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 …
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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