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Iron Sequestration and Anemia of Inflammation
Open accessAbstract
Anemia of chronic disease, also called anemia of inflammation, is characterized by hypoferremia due to iron sequestration that eventually results in iron-restricted erythropoiesis. During the last decade, the molecular mechanisms of iron sequestration have been found to center on cytokine-stimulated overproduction of the iron-regulatory hormone hepcidin. The inflammatory cytokine interleukin-6 (IL-6) is a particularly prominent inducer of hepcidin, but other cytokines are likely to contribute as well. Hepcidin excess causes the endocytosis and proteolysis of the sole known cellular iron exporter, ferroportin, trapping iron in macrophages and iron-absorbing enterocytes. The supply of iron to hemoglobin synthesis becomes limiting, eventually resulting in anemia. Depending on the details of the underlying disease, other inflammation-related mechanisms may also contribute to anemia.
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“A dysfunctional or deregulated iron metabolism in cancer patients often results in a decreased red blood cell (RBC) count [14] and anemia is detected in approximately 40–70% of all cancer patients [15,16].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [14]
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“Iron sequestration in macrophages is a described hallmark of the AI and is an efficient mechanism to quickly deplete iron in the serum to limit the growth of extracellular pathogens (5).”
From Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in Macrophages during Salmonella Infection (2017) · cites this paper as [5]
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“Two molecules, namely hepcidin (HAMP) and ferroportin (FPN), have been identified to play key roles in decreasing systemic iron level by promoting macrophage iron sequestration during infection (5).”
From Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in Macrophages during Salmonella Infection (2017) · cites this paper as [5]
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Metadata
- Authors
- Ganz, T., & Nemeth, E.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Ganz, Tomas
- Venue
- Seminars in Hematology
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 46
- Issue
- 4
- Pages
- 387-393
- ISSN
- 0037-1963 (ISSN-L)
- PMC
- PMC2755591
- OpenAlex
- W1973938903
- Cited by
- 361
- References
- 85
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 28 · 2023: 21 · 2022: 30 · 2021: 23 · 2020: 32 · 2019: 18 · 2018: 11 · 2017: 18 · 2016: 13 · 2015: 22 · 2014: 22 · 2013: 18 · 2012: 33
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Hematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL091531)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065029)
- 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
- anemia of chronic disease, iron sequestration, hypoferremia, hepcidin, interleukin-6, ferroportin, iron regulatory hormone, iron-restricted erythropoiesis, hemoglobin synthesis
- MeSH terms
- Ferroportin, Anemia, Biological Transport, Erythropoiesis, Hematinics, Hemoglobins, Humans, Inflammation, Iron, Macrophages, Interleukin-6, Enterocytes, Antimicrobial Cationic Peptides, Cation Transport Proteins, Hepcidins
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