Tocilizumab, a humanized anti-interleukin-6 receptor antibody, improved anemia in monkey arthritis by suppressing IL-6-induced hepcidin production.
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.
Hashizume
Misato
M
Product Research Department, Chugai Pharmaceutical Co, Ltd, 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan.
Uchiyama
Yasushi
Y
Horai
Naoto
N
Tomosugi
Naohisa
N
Mihara
Masahiko
M
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D064451:Hepcidins; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008252:Macaca fascicularis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D023181:Antimicrobial Cationic Peptides; D002097:C-Reactive Protein; D003094:Collagen; D064451:Hepcidins; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C545475:hepcidin 25, human; C502936:tocilizumab