Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia

被引：197

作者：

Sasu, Barbra J. ^{[1
]}

Cooke, Keegan S. ^{[1
]}

Arvedson, Tara L. ^{[1
]}

Plewa, Cherylene ^{[2
]}

Ellison, Aaron R. ^{[2
]}

Sheng, Jackie ^{[2
]}

Winters, Aaron ^{[2
]}

Juan, Todd ^{[2
]}

Li, Hongyan ^{[3
]}

Begley, C. Glenn ^{[1
]}

Molineux, Graham ^{[1
]}

机构：

[1] Amgen Inc, Dept Hematol Oncol, Thousand Oaks, CA 91320 USA

[2] Amgen Inc, Dept Prot Sci, Thousand Oaks, CA 91320 USA

[3] Amgen Inc, Dept Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA

来源：

BLOOD | 2010年 / 115卷 / 17期

关键词：

RECOMBINANT-HUMAN-ERYTHROPOIETIN; C-REACTIVE PROTEIN; HEMODIALYSIS-PATIENTS; TRANSGENIC MICE; CHRONIC DISEASE; RHEUMATOID-ARTHRITIS; INTRACELLULAR IRON; DEFICIENCY ANEMIA; MOLECULAR CONTROL; HEPCIDIN;

D O I：

10.1182/blood-2009-09-245977

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Iron maldistribution has been implicated in multiple diseases, including the anemia of inflammation (AI), atherosclerosis, diabetes, and neurodegenerative disorders. Iron metabolism is controlled by hepcidin, a 25-amino acid peptide. Hepcidin is induced by inflammation, causes iron to be sequestered, and thus, potentially contributes to AI. Human hepcidin (hHepc) overexpression in mice caused an iron-deficient phenotype, including stunted growth, hair loss, and iron-deficient erythropoiesis. It also caused resistance to supraphysiologic levels of erythropoiesis-stimulating agent, supporting the hypothesis that hepcidin may influence response to treatment in AI. To explore the role of hepcidin in inflammatory anemia, a mouse AI model was developed with heat-killed Brucella abortus treatment. Suppression of hepcidin mRNA was a successful anemia treatment in this model. High-affinity antibodies specific for hHepc were generated, and hHepc knock-in mice were produced to enable antibody testing. Antibody treatment neutralized hHepc in vitro and in vivo and facilitated anemia treatment in hHepc knock-in mice with AI. These data indicate that antihepcidin antibodies may be an effective treatment for patients with inflammatory anemia. The ability to manipulate iron metabolism in vivo may also allow investigation of the role of iron in a number of other pathologic conditions. (Blood. 2010;115(17):3616-3624)

引用

页码：3616 / 3624

页数：9

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