IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

Elizabeta Nemeth; Seth Rivera; Victoria Gabayan; Charlotte Keller; Sarah Taudorf; Bente K Pedersen; Tomas Ganz

doi:10.1172/JCI20945

IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

Elizabeta Nemeth, Seth Rivera, Victoria Gabayan, Charlotte Keller, Sarah Taudorf, Bente K Pedersen, Tomas Ganz

2195 Citations (Scopus)

Abstract

Hypoferremia is a common response to systemic infections or generalized inflammatory disorders. In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown. Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6-hepcidin axis is responsible for the hypoferremia of inflammation.

Original language	English
Journal	The Journal of clinical investigation
Volume	113
Issue number	9
Pages (from-to)	1271-6
Number of pages	6
ISSN	0021-9738
DOIs	https://doi.org/10.1172/JCI20945
Publication status	Published - May 2004
Externally published	Yes

Keywords

Anemia/etiology
Animals
Antimicrobial Cationic Peptides/biosynthesis
Cell Line
Cells, Cultured
Gene Expression Regulation
Hepatocytes/cytology
Hepcidins
Humans
Inflammation/complications
Interleukin-6/blood
Iron/metabolism
Iron Metabolism Disorders/pathology
Kupffer Cells/cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes/cytology
RNA, Messenger/genetics
Reverse Transcriptase Polymerase Chain Reaction

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10.1172/JCI20945

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title = "IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin",

abstract = "Hypoferremia is a common response to systemic infections or generalized inflammatory disorders. In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown. Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6-hepcidin axis is responsible for the hypoferremia of inflammation.",

keywords = "Anemia/etiology, Animals, Antimicrobial Cationic Peptides/biosynthesis, Cell Line, Cells, Cultured, Gene Expression Regulation, Hepatocytes/cytology, Hepcidins, Humans, Inflammation/complications, Interleukin-6/blood, Iron/metabolism, Iron Metabolism Disorders/pathology, Kupffer Cells/cytology, Mice, Mice, Inbred C57BL, Mice, Knockout, Monocytes/cytology, RNA, Messenger/genetics, Reverse Transcriptase Polymerase Chain Reaction",

author = "Elizabeta Nemeth and Seth Rivera and Victoria Gabayan and Charlotte Keller and Sarah Taudorf and Pedersen, {Bente K} and Tomas Ganz",

year = "2004",

month = may,

doi = "10.1172/JCI20945",

language = "English",

volume = "113",

pages = "1271--6",

journal = "The Journal of clinical investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

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TY - JOUR

T1 - IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

AU - Nemeth, Elizabeta

AU - Rivera, Seth

AU - Gabayan, Victoria

AU - Keller, Charlotte

AU - Taudorf, Sarah

AU - Pedersen, Bente K

AU - Ganz, Tomas

PY - 2004/5

Y1 - 2004/5

N2 - Hypoferremia is a common response to systemic infections or generalized inflammatory disorders. In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown. Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6-hepcidin axis is responsible for the hypoferremia of inflammation.

AB - Hypoferremia is a common response to systemic infections or generalized inflammatory disorders. In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown. Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6-hepcidin axis is responsible for the hypoferremia of inflammation.

KW - Anemia/etiology

KW - Animals

KW - Antimicrobial Cationic Peptides/biosynthesis

KW - Cell Line

KW - Cells, Cultured

KW - Gene Expression Regulation

KW - Hepatocytes/cytology

KW - Hepcidins

KW - Humans

KW - Inflammation/complications

KW - Interleukin-6/blood

KW - Iron/metabolism

KW - Iron Metabolism Disorders/pathology

KW - Kupffer Cells/cytology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Monocytes/cytology

KW - RNA, Messenger/genetics

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1172/JCI20945

DO - 10.1172/JCI20945

M3 - Journal article

C2 - 15124018

SN - 0021-9738

VL - 113

SP - 1271

EP - 1276

JO - The Journal of clinical investigation

JF - The Journal of clinical investigation

IS - 9

ER -

IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

Abstract

Keywords

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