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.
MeSH terms
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Anemia / drug therapy*
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Anemia / etiology
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Anemia / physiopathology
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Animals
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Antimicrobial Cationic Peptides / biosynthesis*
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Arthritis, Experimental / complications
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Arthritis, Experimental / drug therapy*
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Arthritis, Experimental / physiopathology
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C-Reactive Protein / drug effects
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C-Reactive Protein / metabolism
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Cattle
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Collagen / immunology
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Collagen / pharmacology
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Disease Models, Animal
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Female
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Hepcidins
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Humans
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Injections, Intravenous
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Interleukin-6 / antagonists & inhibitors*
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Interleukin-6 / metabolism
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Macaca fascicularis
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Receptors, Interleukin-6 / antagonists & inhibitors*
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Receptors, Interleukin-6 / metabolism
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Recombinant Fusion Proteins / antagonists & inhibitors
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / toxicity
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Treatment Outcome
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antimicrobial Cationic Peptides
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Hepcidins
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Interleukin-6
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RNA, Messenger
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Receptors, Interleukin-6
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Recombinant Fusion Proteins
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hepcidin 25, human
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Collagen
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C-Reactive Protein
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tocilizumab