Journal Article

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

Tomosugi, Naohisa, Hashizume, Misato, Uchiyama, Yasushi, Horai, Naoto, Mihara, Masahiko

2010

Overview

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.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Anemia - drug therapy / Anemia - etiology / Anemia - physiopathology / Animals / Antibodies, Monoclonal - pharmacology / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Antimicrobial Cationic Peptides - biosynthesis / Arthritis, Experimental - complications / Arthritis, Experimental - drug therapy / Arthritis, Experimental - physiopathology / C-Reactive Protein - drug effects / C-Reactive Protein - metabolism / Cattle / Collagen - immunology / Collagen - pharmacology / Disease Models, Animal / Down-Regulation - drug effects / Down-Regulation - physiology / Female / Gene Expression Regulation - drug effects / Gene Expression Regulation - physiology / Hepcidins / Humans / Injections, Intravenous / Interleukin-6 - antagonists & inhibitors / Interleukin-6 - metabolism / Macaca fascicularis / Medicine / Medicine & Public Health / Original Article / Receptors, Interleukin-6 - antagonists & inhibitors / Receptors, Interleukin-6 - metabolism / Recombinant Fusion Proteins - antagonists & inhibitors / Recombinant Fusion Proteins - metabolism / Recombinant Fusion Proteins - toxicity / Rheumatology / RNA, Messenger - drug effects / RNA, Messenger - metabolism / Treatment Outcome