The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; 11 of the 30 sources its claims cite were checked for support.
IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin
Open accessAbstract
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. Methods Macrophage culture.Monocytes from peripheral blood were isolated by centrifugation through Ficoll-Paque (Amersham Pharmacia Biotech, Piscataway, New Jersey, USA) and 46% iso-Nonstandard abbreviations used: anemia of inflammation (AI); Iscove's modified Dulbecco's medium (IMDM); medium from LPS-stimulated macrophages (M-LPS); medium from unstimulated macrophages (M); recombinant human IL-6 (rhIL-6); total iron-binding capacity (TIBC); unsaturated iron-binding capacity (UIBC). Conflict of interest:The authors have declared that no conflict of interest exists.
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Claims the paper makes
11 of 30 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“patients with AI due to inflammatory disorders or infections had markedly increased excretion of urinary hepcidin”
What the sources say
- Supportedcites [12] source
The Results and discussion report elevated urinary hepcidin excretion in patients diagnosed with anemia of inflammation compared with healthy subjects and other patient groups. The same section reports very high excretion in a patient with epididymitis and sepsis, supporting the infection component of the claim. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“decreased serum iron”
What the sources say
- Supportedcites [8] Nicolas, 2002, J. Clin. Invest. source
The Results section reports a twofold decrease in serum iron in wild-type mice 16 hours after turpentine injection (Figure 6a). It also notes that this decrease was not observed in hepcidin-deficient mice. (LLM, conf=0.95)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“injections of turpentine increased hepcidin mRNA”
What the sources say
- Supportedcites [8] Nicolas, 2002, J. Clin. Invest. source
The Results section reports a sixfold increase in liver hepcidin gene expression 16 hours after turpentine injection compared with saline-injected controls. The discussion (p. 1042) explicitly describes this as a sixfold increase in liver hepcidin mRNA in mice. (LLM, conf=0.95)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“strong induction of hepcidin mRNA by IL-6”
What the sources say
- Supportedcites [12] source
The Results and discussion section reports that IL-6 induced hepcidin in primary human hepatocytes within 8 hours, with a 25-fold increase. The Figure 2 caption identifies the measured signal as hepcidin mRNA. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“but not IL-1 α or TNFα”
What the sources say
- Supportedcites [12] source
The Results and discussion section reports that IL-1α and TNF-α did not induce hepcidin mRNA within eight hours in primary human hepatocytes, unlike IL-6. It also notes that IL-1α induced hepcidin mRNA after 24 hours, probably indirectly through IL-6; the claim is consistent with the lack of strong direct induction. (LLM, conf=0.90)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LPS treatment increased hepcidin mRNA levels in primary human hepatocytes”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Anti-TNFα Ab's had no detectable effect in either experiment”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hep3B hepcidin mRNA, however, markedly increased after exposure to M-LPS”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Anti-IL-6 Ab's had similar inhibitory effects when hepatocytes or Hep3B cells were treated with conditioned medium from macrophages exposed to peptidoglycan from Staphylococcus aureus”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in IL-6 KO mice hepcidin mRNA increased ninefold”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 10
- It may state two separate claims as one. 17
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“hepcidin synthesis is regulated by dietary iron and iron stores, as well as by tissue oxygenation”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
Section 3.4 reports increased liver HEPC1 and HEPC2 transcripts in mice given dietary carbonyl iron or injected iron–dextran, supporting regulation by iron excess. The paper does not establish regulation by iron stores specifically, and no passage addresses tissue oxygenation; it measures gene expression rather than hepcidin synthesis directly. (LLM, conf=0.88)
- Partly supportedcites [8] Nicolas, 2002, J. Clin. Invest. sourceExperimental — accuracy not yet measured
The hypoxia results report that reduced tissue oxygenation downregulated hepcidin gene expression in mice. The anemia results show that iron loading increased expression, and the Discussion links iron deficiency to low expression until stores are repleted. The paper does not show that dietary iron itself regulates hepcidin synthesis; it describes hepcidin regulating dietary iron absorption instead. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the turpentine-induced hypoferremia was not observed in hepcidin-deficient mice (8), demonstrating that hepcidin is required for iron sequestration during inflammatory conditions”
What the sources say
- Partly supportedcites [8] Nicolas, 2002, J. Clin. Invest. sourceExperimental — accuracy not yet measured
The results and discussion (p. 1042) report that turpentine lowered serum iron in wild-type mice but not in hepcidin-deficient mice. They establish hepcidin’s role in the inflammatory fall in serum iron, but describe iron sequestration as a proposed mechanism, not one directly demonstrated by that experiment. (LLM, conf=0.84)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“hepcidin mRNA expression was increased in mice with dietinduced or genetically induced iron overload”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
Section 3.4 reports increased liver HEPC1 and HEPC2 transcripts in mice given dietary carbonyl iron, supporting the diet-induced part. The paper does not report increased hepcidin mRNA in genetically iron-overloaded mice; its Introduction instead describes iron overload in USF2 knockout mice that lack hepcidin transcripts. Page numbers are not available in our copy. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“decreased in mice with anemia caused by bleeding or hemolysis or in mice with hypoxemia due to decreased ambient oxygen”
What the sources say
- Supportedcites [8] Nicolas, 2002, J. Clin. Invest. source
In “Hepcidin gene expression is decreased after experimentally induced anemia,” the paper reports reduced liver hepcidin mRNA after bleeding and reduced hepcidin expression after PHZ-induced hemolytic anemia. In “Hepcidin gene expression is tightly controlled by hypoxia,” it reports downregulation in mice exposed to reduced oxygen pressure in a hypobaric chamber. The hypoxic reduction was clear after two and four days, though results varied after twelve days. (LLM, conf=0.93)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“in the most common form of hemochromatosis, that caused by mutations in the HFE gene”
What the sources say
- Not checked — no full text of the sourcecites [11] source
- Could not verifycites [12] sourceExperimental — accuracy not yet measured
The Results and discussion (page unavailable) compare urinary hepcidin in patients with well-controlled hereditary hemochromatosis with levels in patients with anemia of inflammation, but do not say hepcidin production is diminished relative to healthy people. A search for HFE mutations found no passage identifying the hemochromatosis patients as having HFE-related disease. (LLM, conf=0.76)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-6 infusion rapidly increased hepcidin excretion (Figure 4B); within 2 hours after the infusion, urinary hepcidin levels were 7.5-fold higher on average than at 0 hours”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“serum iron decreased on average 34% and transferrin saturation decreased 33% in comparison to preinfusion values”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TNFα markedly suppressed hepcidin mRNA levels by a mechanism that did not involve IL-6 regulation”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“both the effects of LPS on primary human hepatocytes and the effects of M-LPS on Hep3B cells were completely reversed when IL-6-neutralizing Ab's were added”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“median haptoglobin mRNA was 9.3-fold higher in turpentine-treated WT mice but only 1.9-fold higher in IL-6 KO mice”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inflammatory and iron pathways of hepcidin stimulation respond rapidly, with major hepcidin increase detectable within 1 day in both humans and mice”
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“hepcidin mRNA was increased in the livers of LPS-treated mice and in LPS-treated hepatocytes”
What the sources say
- Not checked — no full text of the sourcecites [3] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“There is a single human hepcidin gene whose essential role in iron homeostasis was confirmed by identifying homozygous frameshift or nonsense mutations in affected individuals with severe juvenile hemochromatosis”
What the sources say
- Not checked — no full text of the sourcecites [9] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“in transgenic mice overexpressing hepcidin-1 (4), transplacental and intestinal iron transport was blocked, and the mice died at birth from severe iron deficiency unless given parenteral iron supplementation”
What the sources say
- Not checked — no full text of the sourcecites [4] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations suggest that human hepcidin is the functional equivalent of hepcidin-1 in mice.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Overexpression of the other known murine hepcidin gene, hepcidin-2, had no effect on iron metabolism in mice”
What the sources say
- Not checked — no full text of the sourcecites [6] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Hepcidin production was also diminished in another form of juvenile hemochromatosis due to mutations in the hemojuvelin gene”
What the sources say
- Not checked — no full text of the sourcecites [10] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Hepatic hepcidin mRNA levels in mice were shown to increase in response to increased dietary iron”
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In IL-6 KO mice, however, hepcidin mRNA was suppressed, likely due to the negative regulation of hepcidin synthesis by other acute-phase cytokines”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“changes in serum iron concentrations reflected the pattern of hepcidin induction: turpentine treatment caused serum iron decrease in WT mice, but no change in iron levels was detected in IL-6 KO mice”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the decrease in iron supply becomes a bottleneck for hemoglobin synthesis and eventually results in anemia”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When the rate of iron release from macrophages drops, plasma iron concentrations rapidly decrease”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there are at least three major and distinct pathways of regulation of hepcidin: regulation by inflammation, dependent on IL-6; regulation by iron, dependent on some other factor, perhaps transferrin saturation; and suppression of hepcidin production during hypoxia and anemia”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“transgenic overexpression of IL-6 in mice (36) and repeated administration of IL-6 in rats and cancer patients (33) has been reported to cause anemia”
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
IL-6 KO mice do not produce functional IL-6.
“Two pairs of IL-6 -/- (IL-6 KO) mice on a C57BL/6 background”
The paper relies on this without support.
Hepatic hepcidin mRNA levels reflect hepcidin synthesis or activity.
“Median hepcidin-1 expression in the liver increased 12-fold”
The paper relies on this without support.
Turpentine-induced inflammation in mice is a valid model of human inflammatory hypoferremia.
“we used the turpentine-induced mouse model of inflammation”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“increased concentrations of hepcidin then inhibit ferroportin activity”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [52]
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
“leading to depletion of iron in plasma and extracellular fluid (hypoferremia).”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [52]
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
“As a consequence of this interaction, the absorption of iron from the diet is reduced due to hepcidin mediated reduction of ferroportin expression in enterocytes, thereby resulting in a reduction of circulating iron levels which is further aggravated by the inhibition of iron export from macrophages by the same mechanism (Nemeth et al., 2004a; Kemna et al., 2005; Roy et al., 2007; Theurl et al., 2”
From Iron at the interface of immunity and infection (2014) · cites this paper as Nemeth et al., 2004a
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Infection and inflammation induce hepcidin, predominantly through the effects of the cytokine interleukin-6 (IL-6) [52]”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [52]
The cited source says what the claim attributes to it.
In the citing paper
“Blockade of IL-6 receptor signaling prevented the hepatocyte-derived generation of hepcidin, which interferes with iron absorption (Nemeth et al., 2004”
From Targeting Interleukin-6 Signaling in Clinic (2019) · cites this paper as Nemeth et al., 2004
In the citing paper
“Interleukin-6 (IL-6) is the main cytokine that stimulates hepcidin synthesis during infection19 and inflammation, but other factors can also contribute, including activin B20, type I interferons (IFNs)21,22 and BMP2 (REF. 23).”
From Iron homeostasis in host defence and inflammation (2015) · cites this paper as [19]
In the citing paper
“Proinflammatory cytokines induced by inflammation can stimulate anemia of inflammation by limiting serum iron and increasing cellular iron stores by modulating the expression and activity of various iron regulatory proteins including hepcidin, FPN, ferritin, and the iron importer divalent metal transporter 1 (DMT1) [25–30].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [25]
In the citing paper
“However, hepcidin is overexpressed in inflammatory disease and is an early inflammatory marker [245,341-345].”
In the citing paper
“during an inflammatory episode interleukin-6 (IL-6) signals to the liver to release the hormone hepcidin, which promotes iron accumulation in phagocytic cells by inducing degradation of the iron exporter ferroportin (Fpn1) (Nemeth et al., 2004).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Nemeth et al., 2004
In the citing paper
“The inflammatory increase in hepcidin is mainly caused by increased concentrations of IL-6 (interleukin-6) [19], inducing the transcription of the hepcidin gene through the JAK2/STAT3 [20][21][22] pathway.”
From Iron and infection (2018) · cites this paper as [19]
In the citing paper
“The role of IL-6 is important in many models of infection and inflammation [19,24] but in some models other cytokines may partially replace its stimulatory effect on hepcidin [17].”
From Iron and infection (2018) · cites this paper as [19]
In the citing paper
“One main contributing factor to pathologic iron homeostasis is interleukin (IL)-6 mediated induction of hepcidin expression through the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway [154].”
From Iron in immune cell function and host defense (2021) · cites this paper as [154]
In the citing paper
“During inflammation, HAMP is induced in hepatocytes alongside a battery of other acute‐phase proteins, downstream of interleukin‐6 and toll‐like receptor signalling‐associated pathways. 98”
From The battle for iron in enteric infections (2020) · cites this paper as [98]
In the citing paper
“To correct this, all animals were conditioned on a low-iron diet (2-4 ppm iron; Teklad diet TD.80396, Envigo) for 5-7 days prior to, and throughout the duration of, all experiments.”
From Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia (2017) · cites this paper as [43]
In the citing paper
“Accordingly, IL6 is a key mediator of inflammation-driven iron handling, as it induces the production of hepcidin, the master regulator of iron homeostasis [4].”
In the citing paper
“It has been suggested that the COVID-19 related inflammation may be the main cause of COVID-19 associated iron disorders, as an inflammation-driven dysregulation of iron homeostasis is well established [4, 6, 7].”
In the citing paper
“The study of hepcidin regulation in mice housed under standard conditions is confounded by the high iron content of most commercial mouse chow blends.”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [16]
In the citing paper
“Sustained elevation of hepcidin expression, as occurs in many inflammatory states, results in anemia due to reduced availability of iron for erythropoiesis, a condition previously known as “anemia of chronic disease” and more accurately renamed as “anemia of inflammation” [16,22,23].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [16]
In the citing paper
“In animal models, diverse inflammatory and infectious stimuli, including Streptococcus species, Pseudomonas aeruginosa, Aspergillus fumigatus, influenza, turpentine, and lipopolysaccharide (LPS) robustly induce hepcidin in the liver via the induction of IL-6, resulting in rapid reduction in serum iron levels [16,19–21].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [16]
In the citing paper
“In the context of inflammation, IL-6 and IL-22 stimulate HAMP expression via specific receptors signaling through signal transducer and activator of transcription (STAT)-3, while alpha-1 antitrypsin may do so via HJV and matriptase-2 [69–71].”
From Iron deficiency or anemia of inflammation?: Differential diagnosis and mechanisms of anemia of inflammation (2016) · cites this paper as [70]
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 [19]
In the citing paper
“During neuroinflammation, glial cells are activated, which perturbs iron homoeostasis.34,35”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [35]
In the citing paper
“Serum sTR concentration reflects total erythroid activity and iron status and has been shown to reflect plasma iron turnover and erythroid transferrin uptake if iron deficiency is not present (22,25).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [22]
In the citing paper
“Serum sTR concentration reflects total erythroid activity in rats and humans and has been shown to reflect plasma iron turnover and erythroid transferrin uptake very closely if iron deficiency is not present (22).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [22]
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 [197]
In the citing paper
“In mice, HFE2 is localized to the surface of periportal hepatocytes, and HFE2-mutant mice display iron loading and a striking decrease in hepcidin upregulation in response to increased iron from exogenous sources, compared with controls (217).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [217]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Human iron-supplementation participant count differs
MinorThe Methods section says six volunteers participated in the iron-supplementation study, while the Results section says five subjects took the iron supplements.
“Six healthy volunteers collected first morning urine for 9 days.”
“Five subjects took 65 mg of iron (as ferrous sulfate) for 3 days, and their urinary hepcidin was monitored before, during, and after iron supplementation.”
Citations
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Hepcidin, a urinary antimicrobial peptide synthesized in the liver
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Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
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Self-citationHepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
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Self-citationLEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity
Krause, A., Neitz, S., Mägert, H.-J., Schulz, A., Forssmann, W.-G., Schulz-Knappe, P., & Adermann, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01920-7 · Cited by 1,324
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282
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Jahandideh, B., Derakhshani, M., Abbaszadeh, H., Movassaghpour, A. A., Mehdizadeh, A., Talebi, M., & Yousefi, M. (2020) · Human Immunology · doi:10.1016/j.humimm.2020.01.004 · Cited by 65
Old and New Aspects of H. pylori-Associated Inflammation and Gastric Cancer
Dinca, A. L., Meliţ, L. E., & Mărginean, C. O. (2022) · Children · doi:10.3390/children9071083 · Cited by 64
“IL-6 • Expressed by multiple human cells, such as monocytes, lymphocytes, macrophages, and endothelial and intestinal epithelial cells [50] • Essential mediator of both immunity and inflammation [50,51] • Stimulation of acute-phase reactants [52] • A direct association between serum IL-6 levels and the risk or severit…”
Backgroundvon Drygalski, A., & Adamson, J. W. (2012) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607112459648 · Cited by 66
Johnson, D., Bayele, H. K., Johnston, K. L., Tennant, J. P., Srai, S. K., & Sharp, P. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.07.081 · Cited by 60
Altered nutrient status reprograms host inflammation and metabolic health via gut microbiota
Golonka, R. M., Xiao, X., Abokor, A. A., Joe, B., & Vijay–Kumar, M. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108360 · Cited by 60
“IL-6), where IL-6, in particular, promotes the expression of hepcidin, later leading to the degradation of Fpn and thus, induction of hypoferremia [137].”
BackgroundIron regulation by hepatocytes and free radicals
Takami, T., & Sakaida, I. (2011) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.10-76 · Cited by 60
Arndt, S., Maegdefrau, U., Dorn, C., Schardt, K., Hellerbrand, C., & Bosserhoff, A. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.09.048 · Cited by 60
Iron deficiency in critically ill patients: highlighting the role of hepcidin
Heming, N., Montravers, P., & Lasocki, S. (2011) · Critical Care · doi:10.1186/cc9992 · Cited by 61
“The molecular mechanisms implicated in these complex regulations are not fully understood (see [12] for review), but the induction of hepcidin synthesis by inflammation has been shown to be interleukin (IL)-6 dependent [14].”
BackgroundIsoda, M., Hanawa, H., Watanabe, R., Yoshida, T., Toba, K., Yoshida, K., Kojima, M., Otaki, K., Hao, K., Ding, L., et al. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2009.04.009 · Cited by 60
Serum Hepcidin and Iron Absorption in Paediatric Inflammatory Bowel Disease
Martinelli, M., Strisciuglio, C., Alessandrella, A., Rossi, F., Auricchio, R., Campostrini, N., Girelli, D., Nobili, B., Staiano, A., Perrotta, S., et al. (2016) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjv242 · Cited by 60
Sim, M., DAWSON, B. T., Landers, G. J., Wiegerinck, E. T. G., Swinkels, D. W., Townsend, M. A., Trinder, D., & Peeling, P. (2011) · European Journal of Applied Physiology · doi:10.1007/s00421-011-2156-0 · Cited by 60
“However, elevated hepcidin levels have been reported to prevent iron recycling by the macrophages (Nemeth et al. 2004b), and this might explain the decrease in serum iron levels 3 and 24 h post-run in both the CHO and PLA conditions seen here.”
InfluentialTransferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses
Choe, H., Jemielity, S., Abraham, J., Radoshitzky, S. R., & Farzan, M. (2011) · Current Opinion in Microbiology · doi:10.1016/j.mib.2011.07.014 · Cited by 61
“Second, low serum iron, as a result of iron sequestration during infection or tissue damage (‘hypoferremia of inflammation’), can drive TfR1 expression higher [25,26].”
BackgroundIron and platelets: A subtle, under‐recognized relationship
Brissot, É., Troadec, M., Loréal, O., & Brissot, P. (2021) · American Journal of Hematology · doi:10.1002/ajh.26189 · Cited by 60
Management of anemia of inflammation in the elderly
Macciò, A., & Madeddu, C. (2012) · Anemia · doi:10.1155/2012/563251 · Cited by 60
“This finding suggests that hepcidin is strongly involved in iron restriction through reduced absorbance at the duodenal level and the blockage of its release by macrophages, thus leading to a rapid drop in plasma iron levels, ironrestricted erythropoiesis, and anemia [80].”
BackgroundTisi, M. C., Bozzoli, V., Giachelia, M., Massini, G., Ricerca, B. M., Maiolo, E., D’Alo’, F., Larocca, L. M., Piciocchi, A., Tjalsma, H., et al. (2014) · Leukemia & Lymphoma · doi:10.3109/10428194.2013.802314 · Cited by 59
Liu, L., Yu, Z., Cheng, H., Mao, X., Sui, W., Deng, S., Wei, X., Lv, J., Du, C., Xu, J., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-77450-y · Cited by 59
Iron Regulatory Hormone Hepcidin Decreases in Chronic Heart Failure Patients With Anemia
Matsumoto, M., Tsujino, T., Lee‐Kawabata, M., Naito, Y., Akahori, H., Sakoda, T., Ohyanagi, M., Tomosugi, N., & Masuyama, T. (2010) · Circulation Journal · doi:10.1253/circj.cj-09-0663 · Cited by 59
Dao, M. C., & Meydani, S. N. (2013) · Advances in Nutrition · doi:10.3945/an.113.004424 · Cited by 59
“Chronic or acute inflammation also induces hepcidin expression (4,5,17).”
BackgroundInterleukin-6 Contributes to the Development of Anemia in Juvenile CKD
Akchurin, O. M., Patiño, E., Dalal, V., Meza, K., Bhatia, D., Brovender, S., Zhu, Y., Cunningham–Rundles, S., Perelstein, E. M., Kumar, J., et al. (2018) · Kidney International Reports · doi:10.1016/j.ekir.2018.12.006 · Cited by 59
“IL-6 is one of the main described activators of hepcidin in anemia of inflammation.(24) In our experiments, Il6KO CKD(þ) mice had significantly lower serum hepcidin than WT CKD(þ) mice.”
BackgroundIron homeostasis in older adults: balancing nutritional requirements and health risks
Zeidan, R. S., Martenson, M. S., Tamargo, J. A., McLaren, C., Ezzati, A., Lin, Y., Yang, J. J., Yoon, H., McElroy, T., Collins, J. F., et al. (2024) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2024.100212 · Cited by 59
The battle for iron in enteric infections
Sousa Gerós, A., Simmons, A., Drakesmith, H., Aulicino, A., & Frost, J. N. (2020) · Immunology · doi:10.1111/imm.13236 · Cited by 58
Modulation of hepcidin to treat iron deregulation: potential clinical applications
Blanchette, N. L., Manz, D. H., Torti, F. M., & Torti, S. V. (2015) · Expert Review of Hematology · doi:10.1586/17474086.2016.1124757 · Cited by 59
“[28] Mass spectrometry (MS) methods, including time-offlight MS and high performance liquid chromatographytandem MS, have also been used for the detection of”
BackgroundMethodInfluentialTarifeño-Saldivia, E., Aguilar, A., Contreras, D., Mercado, L. A., Lange, B. M., Márquez, K., Henríquez, A., Riquelme-Vidal, C., & Boltaña, S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01296 · Cited by 59
“Transcription of hepcidin gene is upregulated by high iron levels, infection and inflammation (64, 65), being released mainly by the liver and reducing iron export by binding to the iron exporter ferroportin-1 (3).”
BackgroundCellular sensing and transport of metal ions: implications in micronutrient homeostasis
Bird, A. J. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.08.002 · Cited by 60
“HAMP gene expression is also tightly regulated by a number of additional factors including inflammation, erythropoiesis, anemia and hypoxia [100–103].”
BackgroundHepcidin: A Critical Regulator of Iron Metabolism during Hypoxia
Hintze, K. J., & McClung, J. P. (2011) · Advances in Hematology · doi:10.1155/2011/510304 · Cited by 61
“IL-6 mediates hepcidin induction by increasing the binding of the transcription factor STAT3 to hepcidin promoter [20–22].”
BackgroundDysregulated myelopoiesis and hematopoietic function following acute physiologic insult
Loftus, T. J., Mohr, A. M., & Moldawer, L. L. (2017) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000395 · Cited by 58
Abreu, R. B., Quinn, F. D., & Giri, P. K. (2018) · Blood Advances · doi:10.1182/bloodadvances.2017015255 · Cited by 58
“Hepcidin expression in macrophages is independent of IL-6 signaling Hepcidin expression during infection is mostly IL-6 dependent in hepatocytes.(13,31) Therefore, we speculate that after TLR stimulation, macrophages release proinflammatory cytokines such as IL-6 and IL-8, which could be involved in TLR activation–med…”
BackgroundChapter 6 Iron Homeostasis and Erythropoiesis
Wrighting, D. M., & Andrews, N. C. (2008) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(07)00006-3 · Cited by 59
Anaemia, iron homeostasis and pulmonary hypertension: a review
Sonnweber, T., Pizzini, A., Tancevski, I., Löffler‐Ragg, J., & Weiß, G. (2020) · Internal and Emergency Medicine · doi:10.1007/s11739-020-02288-1 · Cited by 59
“Vice versa, IL6 stimulates hepcidin expression via the STAT3 pathway thereby causing intracellular iron sequestration [50].”
BackgroundPaesano, R., Pietropaoli, M., Gessani, S., & Valenti, P. (2008) · Biochimie · doi:10.1016/j.biochi.2008.06.004 · Cited by 59
“In particular, interleukin-6 (IL-6) and probably other cytokines, induce transcription of the hepcidin gene in hepatocytes [30].”
BackgroundIron deficiency impairs Intra-hepatic lymphocyte mediated immune response
Bonaccorsi-Riani, E., Danger, R., Lozano, J. J., Martinez-Picola, M., Kodela, E., Mas-Malavila, R., Bruguera, M., Collins, H. L., Hider, R. C., Martinez-Llordella, M., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0136106 · Cited by 57
“Inflammatory cytokines induce a rapid increase of hepcidin [1], the central mediator of iron homeostasis, which reduces iron export from enterocytes, hepatocytes and, most importantly, macrophages [2].”
BackgroundHepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coli
Houamel, D., Ducrot, N., Lefèbvre, T., Daher, R., Moulouel, B., Sari, M., Lettéron, P., Lyoumi, S., Millot, S., Tourret, J., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014101035 · Cited by 57
Liver expression of hepcidin and other iron genes in two mouse models of beta-thalassemia.
Franceschi, L. D., Daraio, F., Filippini, A., Carturan, S., Muchitsch, E. M., Roetto, A., & Camaschella, C. (2006) · PubMed · Cited by 57
Hepcidin and Cytokines in Anaemia
Means, R. T. (2004) · Hematology · doi:10.1080/10245330400018540 · Cited by 57
“TNF was shown to down regulate hepcidin message expression, and IL-1 had no effect [39].”
BackgroundResultInfluentialBadenhorst, C. E., Dawson, B., Cox, G. R., Laarakkers, C. M., Swinkels, D. W., & Peeling, P. (2015) · European Journal of Applied Physiology · doi:10.1007/s00421-015-3252-3 · Cited by 57
“During periods of elevated hepcidin activity, Fpn channels are internalized and degraded, inhibiting the absorption of iron from the diet, and the recycling of iron from macrophage activity (Nemeth et al. 2004b).”
InfluentialDisorders associated with systemic or local iron overload: from pathophysiology to clinical practice
Sebastiani, G., & Pantopoulos, K. (2011) · Metallomics · doi:10.1039/c1mt00082a · Cited by 58
Lieblein‐Boff, J. C., McKim, D. B., Shea, D. T., Wei, P. Y., Deng, Z., Sawicki, C. M., Quan, N., Bilbo, S. D., Bailey, M. T., McTigue, D. M., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0708-13.2013 · Cited by 57
“Hepcidin decreases serum iron by inhibiting the iron transport channel, ferroportin, which is responsible for the exocytosis of cellular iron stores (Nemeth et al., 2004a).”
BackgroundInfluentialThe struggle for iron: gastrointestinal microbes modulate the host immune response during infection
Markel, T. A., Crisostomo, P. R., Wang, M., Herring, C. M., Meldrum, K. K., Lillemoe, K. D., & Meldrum, D. R. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0906579 · Cited by 57
“Its expression is increased in inflammation and sepsis, thereby leading to the down-regulation of iron absorption, likely through IL-6-dependent mechanisms [103].”
BackgroundChallenging the Validity of the EPO Index
Kaysen, G. A., Müller, H. G., Ding, J., & Chertow, G. M. (2005) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2005.09.013 · Cited by 57
Scheers, N. (2013) · Nutrients · doi:10.3390/nu5030957 · Cited by 59
“In these conditions, increased hepcidin levels are caused by activation of the JAK/STAT pathway mediated by the inflammatory cytokine IL-6 [35].”
BackgroundInfluentialShanmugam, N. K. N., Chen, K., & Cherayil, B. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.689190 · Cited by 57
HMGB1 Mediates Anemia of Inflammation in Murine Sepsis Survivors
Valdés‐Ferrer, S. I., Papoin, J., Dancho, M. E., Olofsson, P. S., Li, J., Lipton, J. M. M., Avancena, P., Yang, H., Zou, Y.-R., Chavan, S. S., et al. (2015) · Molecular Medicine · doi:10.2119/molmed.2015.00243 · Cited by 57
Factors influencing the post-exercise hepcidin-25 response in elite athletes
Peeling, P., McKay, A. K. A., Pyne, D. B., Guelfi, K. J., McCormick, R., Laarakkers, C. M., Swinkels, D. W., Garvican‐Lewis, L. A., ROSS, M. L. R., Sharma, A. P., et al. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3611-3 · Cited by 57
Zhang, V., Nemeth, E., & Kim, A. (2019) · Pharmaceuticals · doi:10.3390/ph12010030 · Cited by 57
“Hepcidin production is stimulated by increases in plasma iron or iron stores, and during times of inflammation [13,14].”
BackgroundSelf-citationIron Metabolism and Its Disorders
Harvey, J. W. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-370491-7.00009-x · Cited by 57
Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies
Tyrrell, J., & Callaghan, M. (2016) · Microbiology · doi:10.1099/mic.0.000220 · Cited by 56
Vitamin A Modulates the Expression of Genes Involved in Iron Bioavailability
Citelli, M., Bittencourt, L. L. D. A., da Silva, S. V., Pierucci, A. P. T. R., & Pedrosa, C. (2012) · Biological Trace Element Research · doi:10.1007/s12011-012-9397-6 · Cited by 57
“Moreover, inflammation can also lead to hepcidin production through the direct activation of toll-like receptors [36] or through inflammatory cytokines such as interleukin-6 [37].”
BackgroundAnemia and pregnancy: A link to maternal chronic diseases
Gangopadhyay, R., Karoshi, M., & Keith, L. (2011) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(11)60005-2 · Cited by 56
“The pathophysiologic mechanism of anemia in diabetes is thought to be mediated through a combination of dietary iron deficiency, functional iron deficiency due to IL-6 and hepcidin activities, erythropoietin deficiency/hyporesponsiveness, and the action of ACE inhibitor and angiotensin receptor antagonists [28].”
BackgroundIs the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?
Harrison-Findik, D.-D. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.1186 · Cited by 56
Anemia in Inflammatory Bowel Disease: An Under-Estimated Problem?
Rogler, G., & Vavricka, S. R. (2015) · Frontiers in Medicine · doi:10.3389/fmed.2014.00058 · Cited by 56
Iron homeostasis and inherited iron overload disorders: an overview
Heeney, M. M., & Andrews, N. C. (2004) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2004.06.018 · Cited by 56
Stoffel, N. U., Lazrak, M., Bellitir, S., Mir, N. E., Hamdouchi, A. E., Barkat, A., Zeder, C., Moretti, D., Aguenaou, H., & Zimmermann, M. B. (2019) · Haematologica · doi:10.3324/haematol.2018.208645 · Cited by 56
“Previous experimental human studies have examined the hepcidin response to inflammation.(10,11) In healthy adults given an infusion of IL-6 (iron status was not reported but subjects were presumably non-anemic), after 2 h urinary hepcidin increased 7.”
BackgroundCzaya, B., Heitman, K., Campos, I., Yanucil, C., Kentrup, D., Westbrook, D., Gutierrez, O., Babitt, J. L., Jung, G., Salusky, I. B., et al. (2022) · eLife · doi:10.7554/elife.74782 · Cited by 56
Exercise-Induced Changes in Iron Status and Hepcidin Response in Female Runners
Auersperger, I., Škof, B., Leskošek, B., Knap, B., Jerin, A., & Lainščak, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058090 · Cited by 55
“inflammation, hypoxia, elevated iron levels), it is likely that hepcidin acts beyond the acute phase [11].”
BackgroundBoutou, A., Karrar, S., Hopkinson, N. S., & Polkey, M. I. (2012) · Respiration · doi:10.1159/000338792 · Cited by 56
Yokota, S., Tanaka, T., & Kishimoto, T. (2012) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x12455960 · Cited by 55
“This leads to hypoferremia and anemia of chronic inflammation [Nemeth et al. 2004; Ganz and Nemeth, 2011].”
BackgroundResistance of dialyzed patients to erythropoietin
Alves, M. T., Villaça, S. S., Ferriani, M. D. G. C., Fernandes, A. P., Dusse, L. M. S., & Gomes, K. B. (2015) · Revista Brasileira de Hematologia e Hemoterapia · doi:10.1016/j.bjhh.2015.02.001 · Cited by 55
Liu, Y., Duan, C., Dai, R., & Zeng, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.739392 · Cited by 58
“Meanwhile, it has been demonstrated that interleukin (IL)-6 generated by cancerassociated fibroblasts (CAFs), TAMs, and neutrophils enhances hepcidin expression, thereby boosting the iron concentration in breast cancer cells (Nemeth et al., 2004; Blanchette-Farra et al., 2018).”
BackgroundCurrent status and prospects of IL-6–targeting therapy
Narazaki, M., & Kishimoto, T. (2022) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2022.2097905 · Cited by 55
The utility of iron chelators in the management of inflammatory disorders
Lehmann, C., Islam, S., Jarosch, S., Zhou, J., Hoskin, D., Greenshields, A., Al-Banna, N., Sharawy, N., Sczcesniak, A., Kelly, M., et al. (2015) · Mediators of Inflammation · doi:10.1155/2015/516740 · Cited by 54
“To mitigate iron losses from the body from shedding of epithelial cells and menstruation, the body must absorb an equivalent amount of iron from the gut, maintaining an overall iron balance.”
BackgroundSerum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease
Mecklenburg, I., Reznik, D., Fasler-Kan, E., Drewe, J., Beglinger, C., & Hruz, P. (2014) · Journal of Crohn's and Colitis · doi:10.1016/j.crohns.2014.04.008 · Cited by 54
Iron Handling in Tumor-Associated Macrophages—Is There a New Role for Lipocalin-2?
Jung, M., Weigert, A., Mertens, C., Rehwald, C., & Brüne, B. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01171 · Cited by 54
“In addition, bacteria-derived LPS and pro-inflammatory cytokines cause macrophages to express hepcidin (83), which degrades FPN and adds to restrain iron.”
BackgroundIntestinal expression of genes implicated in iron absorption and their regulation by hepcidin
Bergamaschi, G., Sabatino, A. D., Pasini, A., Ubezio, C., Costanzo, F., Grataroli, D., Masotti, M., Alvisi, C., & Corazza, G. R. (2016) · Clinical Nutrition · doi:10.1016/j.clnu.2016.09.021 · Cited by 54
Molecular and clinical aspects of iron homeostasis: from anemia to hemochromatosis
Nairz, M., & Weiß, G. (2006) · Wiener klinische Wochenschrift · doi:10.1007/s00508-006-0653-7 · Cited by 54
Protection of intestinal injury during heat stroke in mice by interleukin‐6 pretreatment
Phillips, N. A., Welc, S. S., Wallet, S. M., King, M. A., & Clanton, T. L. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.283416 · Cited by 54
“For example, it is the chief hormone regulating the release of acute phase proteins from the liver, which is critical for surviving invasion of pathogens or in responding to injury or physical stress (Heinrich et al. 1990; Heath et al. 1993; Nemeth et al. 2004).”
BackgroundBenefits and risks of iron therapy for chronic anaemias
Weiss, G., & Gordeuk, V. R. (2005) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2005.01529.x · Cited by 54
Akizawa, T., Nangaku, M., Yamaguchi, T., Koretomo, R., Maeda, K., Miyazawa, Y., & Hirakata, H. (2021) · Kidney Diseases · doi:10.1159/000517053 · Cited by 54
The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
Ravindranath, M. H., Hilali, F. E., & Filippone, E. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.667834 · Cited by 54
Langer, A. L., & Ginzburg, Y. Z. (2017) · Hemodialysis International · doi:10.1111/hdi.12543 · Cited by 57
Iron status in athletic females, a shift in perspective on an old paradigm
Badenhorst, C. E., Goto, K., O’Brien, W. J., & Sims, S. T. (2021) · Journal of Sports Sciences · doi:10.1080/02640414.2021.1885782 · Cited by 54
Treatment of chronic myeloid leukemia in blast crisis
Hehlmann, R., & Saußele, S. (2008) · Haematologica · doi:10.3324/haematol.2008.001214 · Cited by 53
Hepcidin: another culprit for complications in patients with chronic kidney disease?
Nakanishi, T., Hasuike, Y., Otaki, Y., Kida, A., Nonoguchi, H., & Kuragano, T. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfr410 · Cited by 53
“These values are consistent with estimates of plasma hepcidin concentrations based on urinary hepcidin excretion in conditions of iron loading or inflammation [10, 34] and are comparable to circulating hepcidin levels in humans [35, 36].”
ResultMolecular insights into the pathogenesis of hereditary haemochromatosis
Pietrangelo, A. (2006) · Gut · doi:10.1136/gut.2005.078063 · Cited by 53
Beaumont, C., & Canonne‐Hergaux, F. (2005) · Transfusion Clinique et Biologique · doi:10.1016/j.tracli.2005.04.017 · Cited by 57
Hepcidin, iron, and bacterial infection
Barton, J. C., & Acton, R. T. (2019) · Vitamins and hormones · doi:10.1016/bs.vh.2019.01.011 · Cited by 53
Decreased expression of ferroportin in prostate cancer
Xue, D., Zhou, C., Shi, Y., Lü, H., & He, X. (2015) · Oncology Letters · doi:10.3892/ol.2015.3363 · Cited by 53
“It has been reported that hepcidin is closely associated with infection, tumor and chronic inflammation (6).”
Jaeggi, T., Moretti, D., Kvalsvig, J. D., Holding, P., Tjalsma, H., Kortman, G. A. M., Joosten, I., Mwangi, A. M., & Zimmermann, M. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057513 · Cited by 53
“infection, inflammation and iron overload [2,6–8].”
Bansal, S. S., Abbate, V., Bomford, A. B., Halket, J. M., Macdougall, I. C., Thein, S. L., & Hider, R. C. (2010) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.4512 · Cited by 53
Chronic Adherence to a Ketogenic Diet Modifies Iron Metabolism in Elite Athletes
MCKAY, A. K. A., PEELING, P., PYNE, D. B., WELVAERT, M., TEE, N., LECKEY, J. J., SHARMA, A. P., ROSS, M. L. R., GARVICAN-LEWIS, L. A., SWINKELS, D. W., et al. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001816 · Cited by 53
“The role of IL-6 however, extends beyond that of hepatic glucose regulation, also being a key regulator of hepcidin activity (10), particularly during the acute post-exercise recovery period (16).”
BackgroundCostas, B., Couto, A., Azeredo, R., Machado, M., Krogdahl, Å., & Oliva‐Teles, A. (2014) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2014.05.032 · Cited by 53
Marques, O., Horvat, N. K., Zechner, L., Colucci, S., Sparla, R., Zimmermann, S., Neufeldt, C. J., Altamura, S., Qiu, R., Müdder, K., et al. (2024) · Blood · doi:10.1182/blood.2023023417 · Cited by 55
Diet-induced obesity leads to decreased hepatic iron storage in mice
Chung, J., Kim, M. S., & Han, S. N. (2011) · Nutrition Research · doi:10.1016/j.nutres.2011.09.014 · Cited by 54
“Hepcidin expression is suppressed by iron deficiency, anemia, and hypoxia and is strongly induced by inflammation [10,11].”
BackgroundKim, S., Stewart, R. J., Park, W.-Y., Jhon, M., Lee, J., Kim, S., Kim, J., Amminger, G. P., Chung, Y., & Yoon, J. (2018) · Nutrients · doi:10.3390/nu10111707 · Cited by 52
“Inflammation-induced hypoferremia may disrupt brain development, leading to functional defects in adulthood that are synonymous with psychiatric disorders such as schizophrenia 8 [52].”
BackgroundIncrease of Hemoglobin Levels by Anti-IL-6 Receptor Antibody (Tocilizumab) in Rheumatoid Arthritis
Hashimoto, M., Fujii, T., Hamaguchi, M., Furu, M., Ito, H., Terao, C., Yamamoto, K., Yamamoto, W., Matsuo, T., Mori, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098202 · Cited by 53
“IL-6 was the necessary and sufficient cytokine for the induction of hepcidin during inflammation because IL-6 or hepcidin knockout mice do not develop anemia upon inflammation [23] [25].”
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“Conversely, a main mechanism driving ACD is the interleukins-6 release from the inflamed intestine that can trigger increased hepcidin hepatic synthesis, which potentially decreased duodenal absorption of iron and retained iron within cells of the reticular-endothelial system [23].”
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“The indicators of iron status and inflammation markers were selected according to WHO/China CDC expert consultation(24) and WHO report(21) recommendation and previous study.(22,26,27) Every tenth serum sample was measured twice (correlation coefficient of duplicate measurements was 0.”
MethodPhenotypic expression in detected C282Y homozygous women depends on body mass index
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“Indeed, it is tempting to speculate that overweight-related chronic inflammatory state [9] could allow for an increased production of IL-6 which, in turn, could upregulate the hepcidin gene and result in compensating, at least partly, the defect of hepcidin synthesis due to the HFE mutation [10–12].”
BackgroundMycobiota and diet-derived fungal xenosiderophores promote Salmonella gastrointestinal colonization
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Novel therapies in acute and chronic heart failure
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Oncostatin M is a potent inducer of hepcidin, the iron regulatory hormone
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Iron Metabolism in Normal and Pathological Pregnancies and Fetal Consequences
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Iron Metabolism: Interactions with Energy and Carbohydrate Availability
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“5-fold increase in hepcidin concentrations 2 h post-infusion [41].”
Background
Metadata
- Authors
- Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Rigshospitalet (DK)
- Corresponding author
- Ganz, Tomas
- Venue
- Journal of Clinical Investigation
- Published
- 2004-05-01
- Volume
- 113
- Issue
- 9
- Pages
- 1271-1276
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC398432
- OpenAlex
- W2132155262
- Cited by
- 2,650
- References
- 40
- Citations by year
- 2026: 100 · 2025: 97 · 2024: 93 · 2023: 117 · 2022: 115 · 2021: 145 · 2020: 134 · 2019: 130 · 2018: 130 · 2017: 141 · 2016: 103 · 2015: 135 · 2014: 132 · 2013: 140 · 2012: 137
- FWCI
- 55.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- David Geffen School of Medicine, University of California, Los Angeles
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- interleukin-6, hepcidin, iron regulation, inflammation, cytokine signaling, liver, iron regulatory hormone
- MeSH terms
- Anemia, Animals, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Inflammation, Iron, Kupffer Cells, Mice, Inbred C57BL, Monocytes, RNA, Messenger, Interleukin-6, Mice, Knockout, Iron Metabolism Disorders, Reverse Transcriptase Polymerase Chain Reaction, Hepatocytes, Antimicrobial Cationic Peptides, Mice, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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