Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia
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...
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| Veröffentlicht in: | Blood 2010-04, Vol.115 (17), p.3616-3624 |
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| creator | Sasu, Barbra J. Cooke, Keegan S. Arvedson, Tara L. Plewa, Cherylene Ellison, Aaron R. Sheng, Jackie Winters, Aaron Juan, Todd Li, Hongyan Begley, C. Glenn Molineux, Graham |
| description | 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. |
| doi_str_mv | 10.1182/blood-2009-09-245977 |
| format | Article |
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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.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2009-09-245977</identifier><identifier>PMID: 20053755</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Anemia, Iron-Deficiency - drug therapy ; Anemia, Iron-Deficiency - genetics ; Anemia, Iron-Deficiency - immunology ; Anemia, Iron-Deficiency - metabolism ; Anemias. Hemoglobinopathies ; Animals ; Antibodies, Neutralizing - immunology ; Antibodies, Neutralizing - pharmacology ; Antimicrobial Cationic Peptides - antagonists & inhibitors ; Antimicrobial Cationic Peptides - biosynthesis ; Antimicrobial Cationic Peptides - genetics ; Antimicrobial Cationic Peptides - immunology ; Biological and medical sciences ; Brucella abortus ; Disease Models, Animal ; Diseases of red blood cells ; Erythropoiesis - drug effects ; Erythropoiesis - genetics ; Hematologic and hematopoietic diseases ; Hepcidins ; Humans ; Inflammation - complications ; Inflammation - drug therapy ; Inflammation - genetics ; Inflammation - immunology ; Inflammation - metabolism ; Iron - metabolism ; Medical sciences ; Mice ; Mice, Transgenic</subject><ispartof>Blood, 2010-04, Vol.115 (17), p.3616-3624</ispartof><rights>2010 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-eb3a70b2156495d459a2eff2320a555c3f5a132ca4c23fa5baa8b9c28843e5203</citedby><cites>FETCH-LOGICAL-c503t-eb3a70b2156495d459a2eff2320a555c3f5a132ca4c23fa5baa8b9c28843e5203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22745814$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20053755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sasu, Barbra J.</creatorcontrib><creatorcontrib>Cooke, Keegan S.</creatorcontrib><creatorcontrib>Arvedson, Tara L.</creatorcontrib><creatorcontrib>Plewa, Cherylene</creatorcontrib><creatorcontrib>Ellison, Aaron R.</creatorcontrib><creatorcontrib>Sheng, Jackie</creatorcontrib><creatorcontrib>Winters, Aaron</creatorcontrib><creatorcontrib>Juan, Todd</creatorcontrib><creatorcontrib>Li, Hongyan</creatorcontrib><creatorcontrib>Begley, C. Glenn</creatorcontrib><creatorcontrib>Molineux, Graham</creatorcontrib><title>Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia</title><title>Blood</title><addtitle>Blood</addtitle><description>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.</description><subject>Anemia, Iron-Deficiency - drug therapy</subject><subject>Anemia, Iron-Deficiency - genetics</subject><subject>Anemia, Iron-Deficiency - immunology</subject><subject>Anemia, Iron-Deficiency - metabolism</subject><subject>Anemias. Hemoglobinopathies</subject><subject>Animals</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Neutralizing - pharmacology</subject><subject>Antimicrobial Cationic Peptides - antagonists & inhibitors</subject><subject>Antimicrobial Cationic Peptides - biosynthesis</subject><subject>Antimicrobial Cationic Peptides - genetics</subject><subject>Antimicrobial Cationic Peptides - immunology</subject><subject>Biological and medical sciences</subject><subject>Brucella abortus</subject><subject>Disease Models, Animal</subject><subject>Diseases of red blood cells</subject><subject>Erythropoiesis - drug effects</subject><subject>Erythropoiesis - genetics</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hepcidins</subject><subject>Humans</subject><subject>Inflammation - complications</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - genetics</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Iron - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7jj6D0RyEU-t-ZzuvgjL4hcseNFzqE6qMdLpjEl6Yf311jij3oSCkPC8qcoTxp5L8VrKQb2ZlpxDp4QYOypl7Nj3D9hOWjV0QijxkO2EEIfOjL28Yk9q_S6ENFrZx-yKUlb31u7Yz-u1xW949DHElQNtphzueSsILeHaeMphW6Bh5bHklSdsMOUl1kRw4LFynGf0Ld4hP11A_FbxlMKF55nO5gVSghbz2sU1bB4DJTFFeMoezbBUfHZZ9-zr-3dfbj52t58_fLq5vu28Fbp1OGnoxaSkPZjRBnonKOqptBJgrfV6tiC18mC80jPYCWCYRq-GwWi0Sug9e3W-91jyjw1rcylWj8tCY9CwrtfaGjMcDkSaM-lLrrXg7I4lJij3Tgp3ku5-S3cn6Y7qLJ1iLy4Ntilh-Bv6Y5mAlxcAqodlLrD6WP9xqjd2oL_Zs7dnDknHXcTiqo-4krJYyLELOf5_kl_966Jc</recordid><startdate>20100429</startdate><enddate>20100429</enddate><creator>Sasu, Barbra J.</creator><creator>Cooke, Keegan S.</creator><creator>Arvedson, Tara L.</creator><creator>Plewa, Cherylene</creator><creator>Ellison, Aaron R.</creator><creator>Sheng, Jackie</creator><creator>Winters, Aaron</creator><creator>Juan, Todd</creator><creator>Li, Hongyan</creator><creator>Begley, C. Glenn</creator><creator>Molineux, Graham</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100429</creationdate><title>Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia</title><author>Sasu, Barbra J. ; Cooke, Keegan S. ; Arvedson, Tara L. ; Plewa, Cherylene ; Ellison, Aaron R. ; Sheng, Jackie ; Winters, Aaron ; Juan, Todd ; Li, Hongyan ; Begley, C. Glenn ; Molineux, Graham</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-eb3a70b2156495d459a2eff2320a555c3f5a132ca4c23fa5baa8b9c28843e5203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Anemia, Iron-Deficiency - drug therapy</topic><topic>Anemia, Iron-Deficiency - genetics</topic><topic>Anemia, Iron-Deficiency - immunology</topic><topic>Anemia, Iron-Deficiency - metabolism</topic><topic>Anemias. Hemoglobinopathies</topic><topic>Animals</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antibodies, Neutralizing - pharmacology</topic><topic>Antimicrobial Cationic Peptides - antagonists & inhibitors</topic><topic>Antimicrobial Cationic Peptides - biosynthesis</topic><topic>Antimicrobial Cationic Peptides - genetics</topic><topic>Antimicrobial Cationic Peptides - immunology</topic><topic>Biological and medical sciences</topic><topic>Brucella abortus</topic><topic>Disease Models, Animal</topic><topic>Diseases of red blood cells</topic><topic>Erythropoiesis - drug effects</topic><topic>Erythropoiesis - genetics</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hepcidins</topic><topic>Humans</topic><topic>Inflammation - complications</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - genetics</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Iron - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sasu, Barbra J.</creatorcontrib><creatorcontrib>Cooke, Keegan S.</creatorcontrib><creatorcontrib>Arvedson, Tara L.</creatorcontrib><creatorcontrib>Plewa, Cherylene</creatorcontrib><creatorcontrib>Ellison, Aaron R.</creatorcontrib><creatorcontrib>Sheng, Jackie</creatorcontrib><creatorcontrib>Winters, Aaron</creatorcontrib><creatorcontrib>Juan, Todd</creatorcontrib><creatorcontrib>Li, Hongyan</creatorcontrib><creatorcontrib>Begley, C. Glenn</creatorcontrib><creatorcontrib>Molineux, Graham</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sasu, Barbra J.</au><au>Cooke, Keegan S.</au><au>Arvedson, Tara L.</au><au>Plewa, Cherylene</au><au>Ellison, Aaron R.</au><au>Sheng, Jackie</au><au>Winters, Aaron</au><au>Juan, Todd</au><au>Li, Hongyan</au><au>Begley, C. Glenn</au><au>Molineux, Graham</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2010-04-29</date><risdate>2010</risdate><volume>115</volume><issue>17</issue><spage>3616</spage><epage>3624</epage><pages>3616-3624</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>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.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>20053755</pmid><doi>10.1182/blood-2009-09-245977</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anemia, Iron-Deficiency - drug therapy Anemia, Iron-Deficiency - genetics Anemia, Iron-Deficiency - immunology Anemia, Iron-Deficiency - metabolism Anemias. Hemoglobinopathies Animals Antibodies, Neutralizing - immunology Antibodies, Neutralizing - pharmacology Antimicrobial Cationic Peptides - antagonists & inhibitors Antimicrobial Cationic Peptides - biosynthesis Antimicrobial Cationic Peptides - genetics Antimicrobial Cationic Peptides - immunology Biological and medical sciences Brucella abortus Disease Models, Animal Diseases of red blood cells Erythropoiesis - drug effects Erythropoiesis - genetics Hematologic and hematopoietic diseases Hepcidins Humans Inflammation - complications Inflammation - drug therapy Inflammation - genetics Inflammation - immunology Inflammation - metabolism Iron - metabolism Medical sciences Mice Mice, Transgenic |
| title | Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia |
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