The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
Open accessAbstract
Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor α (TNF-α), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation.
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In the citing paper
“However, hepcidin is overexpressed in inflammatory disease and is an early inflammatory marker [245,341-345].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [341]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Cytokines such as interleukin (IL)-1, IL-6, or IL-22 as well as bacterial LPS or endoplasmic reticulum stress induce the formation of the master regulator of iron homeostasis, hepcidin, in the liver (Nemeth et al., 2003; Vecchi et al., 2009; Armitage et al., 2011).”
From Iron at the interface of immunity and infection (2014) · cites this paper as Nemeth et al., 2003
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“patients with AI due to inflammatory disorders or infections had markedly increased excretion of urinary hepcidin”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“but is also an acute phase protein upregulated by inflammatory cytokines, notably IL-6 [18–20].”
From Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans (2015) · cites this paper as [20]
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In the citing paper
“strong induction of hepcidin mRNA by IL-6”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“but not IL-1 α or TNFα”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
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In the citing paper
“in the most common form of hemochromatosis, that caused by mutations in the HFE gene”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
Experimental — accuracy not yet measuredIn the citing paper
“Hepcidin levels are increased during infection and inflammation. Its release is upregulated in response to inflammatory cytokines, in particular interleukin-6 (IL-6) [16–18].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [18]
In the citing paper
“Increased inflammatory activity with reduced intestinal absorption of Fe, with stronger sequestration of Fe in macrophages and lowered Fe, are reflected in the serum, which, at the same time, shows an increase in serum ferritin levels [88,89,90].”
From Iron Deficiency in Obesity and after Bariatric Surgery (2021) · cites this paper as [90]
In the citing paper
“Hepcidin expression is regulated mainly at the level of transcription of the hepcidin (HAMP) gene, being induced in response to: (i) hyperferremia, that is, higher than normal levels of circulating Fe, (ii) cytokines, for example, interleukin (IL)-1, IL-6, and IL-22, or (iii) recognition of bacterial lipopolysaccharide by Toll-like receptor 4 (TLR4) [59][60][61]”
From The Iron age of host–microbe interactions (2015) · cites this paper as [61]
In the citing paper
“During inflammation, hepcidin is induced as an acute-phase reactant by IL-6 and Activin B via STAT3 and SMAD4, respectively (8,9).”
From Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia (2017) · cites this paper as [9]
In the citing paper
“HAMP transcription is induced in hepatocytes in response to i) Fe, ii) microbial sensing by pattern recognition receptors (PRR) or iii) cytokines produced by innate immune cells, including IL-1β, IL-6 or IL-22 (19, 22–24).”
From Innate Nutritional Immunity (2018) · cites this paper as [24]
In the citing paper
“It has been detected and quantitated in urine samples, 91,96 and, with more difficulty, in serum.97”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [96]
In the citing paper
“We found that the hepatocytelike cells of the adenomas expressed very high levels of hepcidin 100 and speculated that our results could be generalized-that induction of hepcidin expression in response to inflammation might explain the anemia of chronic disease.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [96]
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Citations
Cites
Acute-Phase Proteins and Other Systemic Responses to Inflammation
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Research works printed but not linked: 6
- Fleming, 2001, Hepcidin: a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease., Proc Natl Acad Sci U S A., 98, 8160, 10.1073/pnas.161296298 · DOI · Paper page
- Nicolas, 2001, Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice., Proc Natl Acad Sci U S A., 98, 8780, 10.1073/pnas.151179498 · DOI · Paper page
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- Shike, 2002, Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge., Eur J Biochem., 269, 2232, 10.1046/j.1432-1033.2002.02881.x · DOI
- Hunter, 2002, The solution structure of human hepcidin, a peptide-hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis., J Biol Chem., 277, 37597, 10.1074/jbc.M205305200 · DOI · Paper page
- Moshage, 1997, Cytokines and the hepatic acute phase response., J Pathol., 181, 257, 10.1002/(SICI)1096-9896(199703)181:3<257::AID-PATH756>3.0.CO;2-U · DOI
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Metadata
- Authors
- Nemeth, E., Valore, E. V., Territo, M., Schiller, G., Lichtenstein, A., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-04-01
- Volume
- 101
- Issue
- 7
- Pages
- 2461-2463
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2059080581
- Cited by
- 1,417
- References
- 6
- Citations by year
- 2026: 16 · 2025: 31 · 2024: 27 · 2023: 44 · 2022: 41 · 2021: 61 · 2020: 54 · 2019: 56 · 2018: 45 · 2017: 56 · 2016: 51 · 2015: 66 · 2014: 85 · 2013: 82 · 2012: 68
- FWCI
- 35.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, anemia of chronic disease, acute phase proteins, iron overload, iron absorption, iron recycling, serum ferritin, interleukin-6, hepatocytes, inflammation, iron stores
- MeSH terms
- Acute-Phase Proteins, Anemia, Ferritins, Humans, Infections, Inflammation, Interleukin-1, Iron, RNA, Messenger, Tumor Necrosis Factor-alpha, Interleukin-6, Case-Control Studies, Iron Overload, Hepatocytes, Antimicrobial Cationic Peptides, Hepcidins
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