| Project/Area Number |
25461452
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
Nakazawa Soken 大阪大学, 産業科学研究所, 招へい准教授 (00535958)
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| Co-Investigator(Renkei-kenkyūsha) |
Yoshizaki Kazuyuki 大阪大学, 産業科学研究所, 特任教授 (90144485)
Tomosugi Naohisa 金沢医科大学, 医学部, 教授 (80155580)
Kawabata Hiroshi 京都大学, 医学部, 講師 (10329401)
Uno Kazuko (財)ルイ・パストゥール医学研究センター, 研究室室長 (50211082)
TANIGAWA Miki 大阪大学, 産業科学研究所, 研究員
Ito Hiroki 大阪大学, 産業科学研究所, 招へい研究員 (60590635)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 炎症性貧血 / ヘプシジン / IL-6 / 関節リウマチ / フェロポルチン / TNF-a / リウマチ / TNFa / tocilizumab / BMP / TNFα / トシリズマブ |
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| Outline of Final Research Achievements |
The role of hepcidin and its regulation by multiple inflammatory cytokines in patients with anemia of inflammation (AI) is still largely unknown. In this study, by using anti-cytokine biologics as a tool, we investigated the mechanism of AI in patients with rheumatoid arthritis (RA). We found that tocilizumab (an anti-IL-6 receptor antibody) can reduce serum hepcidin and improve anemia in RA patients, but TNF-a inhibitors (TNFi) displayed significantly weaker effects than tocilizumab on suppressing serum hepcidin levels and increase hemoglobin (Hb) levels. And serum hepcidin reduction by TNFi was accompanied by a decrease in serum IL-6 suggesting that TNFi on reduction of hepcidin was indirect. Our findings indicated that IL-6-induced hepcidin mediated iron metabolism contribute to the pathogenesis of RA-related anemia directly. We also identified the novel regulation mechanisms involving IL-6-mediated induction and TNF-a-mediated inhibition of hepcidin production.
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