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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Weiss, G., & Goodnough, L. T. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041809 · Cited by 3,800
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
Self-citationAndrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544
Self-citationHepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
Nemeth, E., Valore, E. V., Territo, M., Schiller, G., Lichtenstein, A., & Ganz, T. (2003) · Blood · doi:10.1182/blood-2002-10-3235 · Cited by 1,417
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
Flagged first, then by citations
Research works printed but not linked: 2
- Means, 1999, Int. J. Hematol., 70, 7
- Barille, 2000, Eur. Cytokine Netw., 11, 546
Cited by
Sorted by citations
Items 1,301–1,400 of 2,683
Hepatic iron storage is related to body adiposity and hepatic inflammation
Park, C. Y., Chung, J., Koo, K.-O., Kim, M. S., & Han, S. N. (2017) · Nutrition & Metabolism · doi:10.1186/s12986-017-0169-3 · Cited by 21
“Lipopolysaccharide (LPS)-treatment increased Hamp mRNA levels in primary hepatocyte, Hep3B, and rat liver tissue [14, 15].”
BackgroundDistinct iron homeostasis in C57BL/6 and Balb/c mouse strains
Saha, P., Xiao, X., Li, Y., Golonka, R. M., Abokor, A. A., Yeoh, B. S., & Vijay–Kumar, M. (2020) · Physiological Reports · doi:10.14814/phy2.14441 · Cited by 21
“, tumor necrosis factor (TNF)-α and interleukin (IL)-6 (Nemeth et al., 2004).”
BackgroundProlyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state
Joharapurkar, A. A., Patel, V. J., Kshirsagar, S. G., Patel, M. S., Savsani, H. H., Kajavadara, C. K., Valani, D., & Jain, M. R. (2022) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2022.100102 · Cited by 21
“These data are consistent with reports indicating that anemia of chronic kidney disease are associated with increased hepcidin (Nemeth et al., 2004).”
BackgroundMethodResultInfluentialAdipocyte Hypoxia Increases Hepatocyte Hepcidin Expression
Hintze, K. J., Snow, D. R., Nabor, D., & Timbimboo, H. (2010) · Biological Trace Element Research · doi:10.1007/s12011-010-8932-6 · Cited by 21
The iron trap: iron, malaria and anemia at the mother–child interface
Friedman, J. F., Kurtis, J. D., Kabyemela, E., Fried, M., & Duffy, P. E. (2009) · Microbes and Infection · doi:10.1016/j.micinf.2009.02.006 · Cited by 21
Silencing of hepcidin enforces the apoptosis in iron-induced human cardiomyocytes
Hsieh, Y., Huang, C.-H., Lee, C.-Y., Lin, C., & Chang, C. (2014) · Journal of Occupational Medicine and Toxicology · doi:10.1186/1745-6673-9-11 · Cited by 21
“The net effect of which is greater intracellular iron storage, along with less iron dietary absorption and circulating availability [9].”
BackgroundHepatic iron metabolism gene expression profiles in HFE associated Hereditary Hemochromatosis
Gleeson, F. C., Ryan, E. M., Barrett, S., Russell, J. L., & Crowe, J. (2006) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2006.09.008 · Cited by 21
Iron chelators: as therapeutic agents in diseases
Salimi, Z., Afsharinasab, M., Rostami, M., Milasi, Y. E., Ezmareh, S. F. M., Sakhaei, F., Mohammad-Sadeghipour, M., Manesh, S. M. R., & Asemi, Z. (2024) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000001717 · Cited by 24
“Iron is trapped in liver cells in this condition, and further uptake is blocked despite low circulating iron levels [131] .”
BackgroundLaparra, J. M., & Haros, C. M. (2016) · Food & Function · doi:10.1039/c5fo01197c · Cited by 21
Iron-Refractory Iron Deficiency Anemia
Keskin, E. Y., & Yenicesu, İ. (2015) · Turkish Journal of Hematology · doi:10.4274/tjh.2014.0288 · Cited by 21
“In ACI, inflammatory cytokines stimulate hepcidin expression, resulting in a decline of iron mobilization from its stores to be used in erythropoiesis [65].”
BackgroundHepcidin and iron parameters in children with anemia of chronic disease and iron deficiency anemia
Mahajan, G., Sharma, S., Chandra, J., & Nangia, A. (2017) · Blood Research · doi:10.5045/br.2017.52.3.212 · Cited by 21
“[6] found that chronic stimulation of the IL-6–hepcidin axis by inflammation is responsible for iron-restricted erythropoiesis.”
BackgroundHematologic Aspects of Kidney Disease
Brugnara, C., & Eckardt, K. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4160-6193-9.10056-9 · Cited by 21
Abioye, A. I., Aboud, S., Premji, Z. G., Etheredge, A. J., Gunaratna, N. S., Sudfeld, C. R., Noor, R. A., Hertzmark, E., Spiegelman, D. L., Duggan, C., et al. (2019) · European Journal of Clinical Nutrition · doi:10.1038/s41430-019-0512-z · Cited by 21
“These findings may also not be generalizable to HIV-infected pregnant women and others at risk of chronic inflammation, which alters iron pathophysiology and biomarker responses [55].”
BackgroundDowsett, J., Didriksen, M., von Stemann, J. H., Larsen, M. H., Thørner, L. W., Sørensen, E., Erikstrup, C., Pedersen, O. B., Hansen, M. B., Eugen‐Olsen, J., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-05658-1 · Cited by 21
Iron deficiency, iron deficiency anaemia and anaemia of inflammation – an overview
Kulik-Rechberger, B., & Dubel, M. (2023) · Annals of Agricultural and Environmental Medicine · doi:10.26444/aaem/171121 · Cited by 21
“N Daily doses are recommended of 10–12.5 mg of elemental iron (equivalent to 50–62.5 mg of ferrous sulfate heptahydrate, 30–37.5 mg of ferrous fumarate and 83.3– 104.2 mg of ferrous gluconate) for 3 consecutive months per year for infants, and children aged 6–23 months, 30 mg for pre-school…”
BackgroundInfluentialCan Iron and Polyunsaturated Fatty Acid Supplementation Induce Ferroptosis?
Delesderrier, E., Monteiro, J. D. C., de Freitas, S. C. V., Pinheiro, I. C., Batista, M. S., & Citelli, M. (2023) · Cellular Physiology and Biochemistry · doi:10.33594/000000620 · Cited by 22
Jacober, M. L. V., Mamoni, R. L., Lima, C. S. P., dos Anjos, B. L., & Grotto, H. Z. W. (2007) · Medical Oncology · doi:10.1007/s12032-007-0009-9 · Cited by 21
Tabbah, S., Buhimschi, C. S., Millen, K. R., Pierson, C. R., Bhandari, V., Samuels, P., & Buhimschi, I. A. (2018) · American Journal of Perinatology · doi:10.1055/s-0038-1626711 · Cited by 20
Hepcidin, haemoglobin and ferritin levels in sickle cell anaemia
Ezeh, C., Ugochukwu, C. C., Weinstein, J., & Okpala, I. E. (2004) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2004.00337.x · Cited by 20
Hemochromatosis gene mutations and iron metabolism in celiac disease.
Barisani, D., Ceroni, S., Bianco, S. D., Meneveri, R., & Bardella, M. T. (2004) · PubMed · Cited by 20
Ceramide Induces Human Hepcidin Gene Transcription through JAK/STAT3 Pathway
Lu, S., Natarajan, S. K., Mott, J. L., Kharbanda, K. K., & Harrison-Findik, D. D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147474 · Cited by 20
“The transcription of hepcidin gene, HAMP has been shown to be activated by the binding of the transcription factor, STAT3 toHAMP promoter [14,15,18].”
BackgroundMilne, D. J., Fernández-Montero, Á., Gundappa, M. K., Wang, T., Acosta, F., Torrecillas, S., Montero, D., Zou, J., Sweetman, J. W., & Secombes, C. J. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.08.005 · Cited by 20
“These AMPs are secreted constitutively at low levels to protect against environmental microbes but are markedly and rapidly upregulated when infection occurs and in response to inflammatory cytokines such as IL-1β, IL-6 and TNF-α (Nemeth et al., 2004; Voss et al., 2005).”
BackgroundAl-Bakheit, A. A., & Abu-Qatouseh, L. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104210 · Cited by 20
Seven days of high carbohydrate ingestion does not attenuate post-exercise IL-6 and hepcidin levels
Badenhorst, C. E., Dawson, B., Cox, G. R., Sim, M., Laarakkers, C. M., Swinkels, D. W., & Peeling, P. (2016) · European Journal of Applied Physiology · doi:10.1007/s00421-016-3426-7 · Cited by 20
“Hepcidin is the iron regulatory hormone responsible for the down-regulation of iron metabolism through the internalisation and degradation of ferroportin export channels within the small intestine and on the cell surface of macrophages (Nemeth et al. 2004b).”
Helfrich, K. K., Saini, N., Kling, P. J., & Smith, S. M. (2017) · Biochemistry and Cell Biology · doi:10.1139/bcb-2017-0206 · Cited by 21
“Normally, upregulated under conditions of iron overload (Nemeth et al. 2004) (see Figure 1), chronic alcohol suppresses liver hepcidin expression, thus limiting ferroportin degradation and increasing dietary absorption despite elevated hepatic iron stores (Bridle et al.”
Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy
Rapalino, O., Pourvaziri, A., Maher, M. D., Jaramillo‐Cardoso, A., Edlow, B. L., Conklin, J., Huang, S. Y., Westover, M. B., Romero, J. M., Halpern, E. F., et al. (2021) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6966 · Cited by 20
“Interleukin 6 has been shown to mediate low iron levels during inflammatory states via the production of hepcidin.(28) These cytokines might also modulate the transcription of the erythropoietin (EPO) gene and inhibit”
BackgroundGrimer, R. J., Gaston, C. L., Carter, S., Tillman, R. M., Abudu, A., Jeys, L. M., Sudo, A., & Nakamura, T. (2013) · Journal of Orthopaedic Science · doi:10.1007/s00776-013-0454-6 · Cited by 20
“Hepcidin is considered to be an iron-regulatory hormone that is responsible for inflammation-induced iron disutilization, resulting in the anaemia associated with acute and chronic infections, chronic kidney disease, and malignant tumours [8].”
BackgroundLiu, S., Suragani, R. N. V. S., Han, A., Zhao, W., Andrews, N. C., & Chen, J.-J. (2008) · Haematologica · doi:10.3324/haematol.12175 · Cited by 20
Harrington-Kandt, R., Stylianou, E., Eddowes, L. A., Lim, P. J., Stockdale, L. K., Pinpathomrat, N., Bull, N. C., Pasricha, J., Ulaszewska, M., Beglov, Y., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191038 · Cited by 21
“Persistent upregulation of hepcidin can lead to anaemia of chronic disease (ACD) [17, 18].”
BackgroundHeme oxygenase and iron status in exosomes of psoriasis patients
El-Rifaie, A.-A., Sabry, D., Doss, R. W., Kamal, M. A., & El-Hassib, D. M. A. (2018) · Archives of Dermatological Research · doi:10.1007/s00403-018-1852-6 · Cited by 21
Lei, L., Liu, S., Ye, Y., Qiu, X., Huang, D., Pan, D., Chen, J., Qian, Z. M., McMillin, S. E., Vaughn, M. G., et al. (2021) · Toxins · doi:10.3390/toxins13110806 · Cited by 20
“IL-6 further stimulates the synthesis of hepcidin [45] by blocking iron absorption and macrophage iron recycling, resulting in iron deficiency and, in turn, anemia [46,47].”
BackgroundZiemann, E., Kasprowicz, K., Kasperska, A., Zembroń-Łacny, A., Antosiewicz, J., & Laskowski, R. (2013) · Europe PMC (PubMed Central) · Cited by 20
Adaptive immunity and vaccination – iron in the spotlight
Preston, A. E., Drakesmith, H., & Frost, J. N. (2021) · Immunotherapy Advances · doi:10.1093/immadv/ltab007 · Cited by 21
“Clinical trial results indicate that therapeutic blockade of IL-6 with drugs such as tocilizumab and sarilumab may improve patient outcome [69, 70].”
BackgroundInfluentialIRON HOMEOSTASIS AND ITS DISORDERS IN MICE AND MEN: POTENTIAL LESSONS FOR RHINOS
Ganz, T., & Nemeth, E. (2012) · Journal of Zoo and Wildlife Medicine · doi:10.1638/2011-0158.1 · Cited by 20
Self-citationBanerjee, S., Katiyar, P., Kumar, L., Kumar, V., Saini, S. S., Krishnan, V., Sircar, D., & Roy, P. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.03.019 · Cited by 20
Meléndez‐Lazo, A., Tvarijonaviciute, A., Cerón, J. M. C., Planellas, M., & Pastor, J. (2015) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2015.01.008 · Cited by 20
Kenawi, M., Rouger, E., Island, M., Leroyer, P., Robin, F., Remy, S., Tesson, L., Anegón, I., Nay, K., Derbré, F., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901106r · Cited by 22
PCB-77 disturbs iron homeostasis through regulating hepcidin gene expression
Wang, L., Zhang, S., Lin, R., Li, L., Zhang, D., Li, X., & Liu, S. (2013) · Gene · doi:10.1016/j.gene.2013.09.023 · Cited by 19
Nielsen, A. B., Hansen, J. W., Ørskov, A. D., Dimopoulos, K., Salem, M., Grigorian, M., Brüünsgaard, H., & Grønbæk, K. (2022) · HemaSphere · doi:10.1097/hs9.0000000000000713 · Cited by 19
Upregulation of iron regulatory hormone hepcidin by interferon α
Ichiki, K., Ikuta, K., Addo, L., Tanaka, H., Sasaki, Y., Shimonaka, Y., Sasaki, K., Ito, S., Shindo, M., Ohtake, T., et al. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12348 · Cited by 19
Update on Safety of ESAs in Cancer-Induced Anemia
Glaspy, J. A. (2012) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2012.0065 · Cited by 19
Das, N. K., Sandhya, S., Vishnu Vivek, G., Kumar, R., Singh, A. K., Bal, S. K., Kumari, S., & Mukhopadhyay, C. K. (2018) · Cellular Microbiology · doi:10.1111/cmi.12834 · Cited by 19
Durigova, A., Lamy, P., Thézenas, S., Pouderoux, S., Montels, F., Romieu, G., Gutowski, M., & Jacot, W. (2013) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2013-0031 · Cited by 19
“Increased hepatic production of hepcidin upon IL6 stimulation inhibits iron duodenal absorption and induces hypoferremia that arises within a few hours after inflammation induction [18, 19].”
BackgroundAnderson, D. S., Kirchner, M., Kellogg, M. D., Kalish, L. A., Jeong, J., Vanasse, G. J., Berliner, N., Fleming, M. D., & Steen, H. (2011) · Analytical Chemistry · doi:10.1021/ac2020905 · Cited by 19
Expression of serum BMP6 and hepcidin in cancer-related anemia
Cheng, Z., Yan, M., Lu, Y., & Pan, X. (2020) · Hematology · doi:10.1080/16078454.2020.1738098 · Cited by 19
Relationships Among Serum Iron, Inflammation, and Body Mass Index in Children
Sharma, A., McKenna, A. M., Lepage, N., Nieuwenhuys, E. J., & Filler, G. (2009) · Advances in Pediatrics · doi:10.1016/j.yapd.2009.08.014 · Cited by 19
Serum Hemojuvelin and Hepcidin Levels in Chronic Kidney Disease
Rumjon, A., Sarafidis, P. A., Brincat, S., Musto, R., Małyszko, J., Bansal, S. S., & Macdougall, I. C. (2012) · American Journal of Nephrology · doi:10.1159/000336528 · Cited by 19
Are Serum Hepcidin Levels Chronically Elevated in Collegiate Female Distance Runners?
Ma, X., Patterson, K., Gieschen, K. M., & Bodary, P. F. (2013) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.23.5.513 · Cited by 19
“This response is mediated by the action of various cytokines including the proinflammatory cytokine interleukin-6 (IL-6), which has been shown to induce HAMP expression (Nemeth et al., 2004).”
InfluentialCan We Personalize Treatment for Kidney Diseases?
Rovin, B. H., McKinley, A. M., & Birmingham, D. J. (2009) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04140609 · Cited by 19
“The most intriguing of these is hepcidin, an iron regulatory peptide hormone mostly made by the liver (50,51); however, hepcidin is regulated by cytokines such as TNF and IL-6, both of which have been implicated in SLE (52–55).”
BackgroundThe Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa
Byakwaga, H., Hunt, P. W., Laker‐Oketta, M., Glidden, D. V., Huang, Y., Bwana, B. M., Mocello, A. R., Bennett, J., Walusansa, V., Dollard, S. C., et al. (2015) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000000747 · Cited by 19
“We also observed that lower hemoglobin was associated with KS which we speculate reflects anemia of chronic inflammation driven by elevated levels of inflammatory cytokines [55, 56] and/or KS involvement of the gastrointestinal tract with occult hemorrhage [57].”
Motalib, T. A., Khalaf, F. A., & El-Hendawy, G. R. (2015) · The Egyptian Journal of Medical Microbiology · doi:10.12816/0024928 · Cited by 19
Hepcidin and Its Role in Iron Homeostasis.
Kwapisz, J., Słomka, A., & Żekanowska, E. (2009) · PubMed Central · Cited by 19
Khorramian, E., Fung, E., Chua, K. J., Gabayan, V. R., Ganz, T., Nemeth, E., & Kim, A. (2017) · Shock · doi:10.1097/shk.0000000000000886 · Cited by 19
“This dietary conditioning was applied because the high iron content of standard chow maximally stimulates hepcidin expression, making it unresponsive to inflammatory stimuli (17).”
BackgroundSelf-citationSignificance of Hyperferritinemia in Hospitalized Adults
Schaffner, M., Rosenstein, L. J., Ballas, Z. K., & Suneja, M. (2017) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2017.04.016 · Cited by 19
DNA methylation of hepatic iron sensing genes and the regulation of hepcidin expression
Sharp, P., Clarkson, R., Hussain, A., Weeks, R. J., & Morison, I. M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0197863 · Cited by 19
Costa, E. M., Fernandes, J. C., Ribeiro, S., Sereno, J., Garrido, P., Rocha‐Pereira, P., Coimbra, S., Catarino, C., Belo, L., Bronze-da-Rocha, E., et al. (2014) · PubMed Central · doi:10.14366/ad.2014.0500356 · Cited by 21
“Furthermore, it is known that increased levels of hepcidin (Hamp) are involved in the pathogenesis of the anemia of inflammation [10,11].”
BackgroundNazif, H. K., El-Shaheed, A. A., & El-Shamy, K. A. (2015) · International Journal of Health Sciences · doi:10.12816/0024114 · Cited by 19
“(8) (9) To strengthen thepossible link between the poor iron status of obesity and hepcidin, there is the interesting observation that hepcidin is expressed not only in the liver but also in adipose tissue and that m RNAexpression is increased in adipose tissue of obese patients.”
BackgroundNemere, I., & Hintze, K. J. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21437 · Cited by 19
“Hepcidin expression is induced in inflammation by interleukin 6 [Nemeth et al., 2004a] and interleukin 1 [Lee et al., 2005] and induction ismediated by STAT3 transcription factor binding to the hepcidin promoter [Wrighting and Andrews, 2006; Verga Falzacappa et al., 2007].”
BackgroundMathematical model of mycobacterium–host interaction describes physiology of persistence
Pedruzzi, G., Rao, K. V. S., & Chatterjee, S. (2015) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.03.031 · Cited by 21
Proteome analysis of biological fluids from autoimmune‐rheumatological disorders
Franceschi, L. D., Bosello, S. L., Scambi, C., Biasi, D., Santis, M. D., Caramaschi, P., Peluso, G., Verde, V. L., Bambara, L. M., & Ferraccioli, G. (2010) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201000069 · Cited by 19
“Hepcidin expression is regulated by IL-6 and tumor necrosis factor-a [96, 97] and both cytokines are known to be involved in LN kidney disease [98].”
BackgroundMemoli, B., Salerno, S., Procino, A., Postiglione, L., Morelli, S., Sirico, M. L., Giordano, F., Ricciardone, M., Drioli, E., Andreucci, V. E., et al. (2010) · Clinical Science · doi:10.1042/cs20090634 · Cited by 20
The small molecule ferristatin II induces hepatic hepcidin expression in vivo and in vitro
Alkhateeb, A. A., Buckett, P. D., Gardeck, A. M., Kim, J., Byrne, S. L., Fraenkel, P. G., & Wessling‐Resnick, M. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00324.2014 · Cited by 19
“Hepcidin expression is transcriptionally regulated by various stimuli including iron (26), hypoxia (22), erythropoiesis (22), and inflammation (20).”
BackgroundShin, J. A., Kim, H.-S., Kang, J. L., & Park, E. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.08.010 · Cited by 19
Jung, M. M., Shen, S., Botten, G. A., Olender, T., Katsumura, K. R., Johnson, K. D., Soukup, A. A., Liu, P., Zhang, Q., Jensvold, Z. D., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci162685 · Cited by 19
“Besides granulopoiesis, high IL-6 induces anemia of inflammation (111, 112).”
Melatonin Regulates Iron Homeostasis by Inducing Hepcidin Expression in Hepatocytes
Park, W., Choi, B., Kim, Y., Kim, Y., Park, M.-J., Kim, D., Choi, H., & Kim, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073593 · Cited by 19
“IL-6-induced hepcidin inhibits the absorption of dietary iron, resulting in hypoferremia, which regulates pathogen survival [11].”
BackgroundHeat stress stimulates hepcidin mRNA expression and C/EBPα protein expression in aged rodent liver
Bloomer, S. A., Kregel, K. C., & Brown, K. E. (2013) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2013.07.012 · Cited by 19
“Hepcidin expression is also induced by inflammatory stressors such as turpentine (Nicolas et al., 2002), lipopolysaccharide (LPS) (Kemna, Pickkers, Nemeth, van der Hoeven, & Swinkels, 2005; Pigeon et al., 2001), and the cytokine, interleukin-6 (IL-6) (Nemeth et al., 2003, 2004a).”
InfluentialZhang, F., zhao, P., Qian, Z., & Zhong, M. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.649640 · Cited by 19
Видиборець, С. В., & Борисенко, Д. (2019) · Science Review · doi:10.31435/rsglobal_sr/30122019/6862 · Cited by 19
Chikazawa, S., Nakazawa, T., Hori, Y., Hoshi, F., Kanai, K., Ito, N., Orino, K., Watanabe, K., & Higuchi, S. (2013) · Journal of Veterinary Medical Science · doi:10.1292/jvms.13-0149 · Cited by 19
Cardiac iron metabolism during aging – Role of inflammation and proteolysis
Walter, S., Mertens, C., Muckenthaler, M. U., & Ott, C. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111869 · Cited by 19
Ferroptosis in Glaucoma: A Promising Avenue for Therapy
Zhu, J., Chen, H., Wu, J., Li, S., Lin, W., Wang, N., & Bai, L. (2024) · Advanced Biology · doi:10.1002/adbi.202300530 · Cited by 19
Zheng, H., Badenhorst, C. E., Lei, T., Liao, Y., Muhamed, A. M. C., Fujii, N., Kondo, N., & Mündel, T. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00014.2021 · Cited by 19
Mild anemia as a single independent predictor of mortality in patients with COVID‐19
Tremblay, D. A., Rapp, J. L., Alpert, N., Lieberman‐Cribbin, W., Mascarenhas, J. O., Taioli, E., & Ghaffari, S. (2021) · eJHaem · doi:10.1002/jha2.167 · Cited by 18
A computational model to understand mouse iron physiology and disease
Parmar, J. H., & Mendes, P. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006680 · Cited by 20
Clinical Immunoassay for Human Hepcidin Predicts Iron Deficiency in First-Time Blood Donors
Gutschow, P., Han, H., Olbina, G., Westerman, K., Nemeth, E., Ganz, T., Copeland, K. A. F., Westerman, M. E., & Ostland, V. E. (2020) · The Journal of Applied Laboratory Medicine · doi:10.1093/jalm/jfaa038 · Cited by 18
“Hepcidin is upregulated by iron loading (10) and inflammation (11) and downregulated by anemia and hypoxia (12).”
BackgroundSelf-citationIron and Clinical Outcomes in Dialysis and Non–Dialysis-Dependent Chronic Kidney Disease Patients
Kovesdy, C. P. (2009) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2008.12.006 · Cited by 18
Katodritou, E., Ganz, T., Terpos, E., Verrou, E., Olbina, G., Gastari, V., Hadjiaggelidou, C., Varthaliti, M., Georgiadou, S., Westerman, M. E., et al. (2009) · American Journal of Hematology · doi:10.1002/ajh.21448 · Cited by 18
Self-citationSerum Prohepcidin and Hepcidin in Hemodialyzed Patients Undergoing Iron Therapy
Małyszko, J., Małyszko, J. S., & Myśliwiec, M. (2009) · Kidney & Blood Pressure Research · doi:10.1159/000235747 · Cited by 18
Johnson, D. W., Hawley, C. M., Rosser, B., Beller, E., Thompson, C., Fassett, R. G., Ferrari, P., MacDonald, S., Pedagogos, E., & Cass, A. (2008) · BMC Nephrology · doi:10.1186/1471-2369-9-8 · Cited by 18
“Abbreviations AKTN: Australasian Kidney Trials Network; CKD: Chronic kidney disease; CRP: C-reactive protein; CTN: Clinical trials notification; DPO: Darbepoetin; EPO: Erythropoietin; ESA: Erythropoiesis stimulating agent; ESKD: End-stage kidney disease; FPN: Ferroportin; HERO: hemoglobin elevation in erythropoietin r…”
BackgroundInfluentialThe effect of the competitive season in professional basketball on inflammation and iron metabolism
Dzedzej, A., Ignatiuk, W., Jaworska, J., Grzywacz, T., Lipińska, P., Antosiewicz, J., Korek, A., & Ziemann, E. (2016) · Biology of Sport · doi:10.5604/20831862.1201811 · Cited by 18
“tor responsible for regulating hepcidin activity [9].”
Gautier, A., Graff, E. C., Bacek, L. M., Fish, E. J., White, A., Palmer, L. E., & Kuo, K. W. (2020) · Frontiers in Veterinary Science · doi:10.3389/fvets.2019.00506 · Cited by 18
Li, L., Ning, D.-S., Fu, Y., & Pan, Z. (2021) · Fitoterapia · doi:10.1016/j.fitote.2021.104949 · Cited by 18
Anämie bei Patienten mit rheumatoider Arthritis
Wahle, M. (2012) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-011-0925-0 · Cited by 18
Çalışkan, Y., Yelken, B., Özkök, A., Görgülü, N., Yazıcı, H., Telci, A., & Yıldız, A. (2012) · BMC Nephrology · doi:10.1186/1471-2369-13-56 · Cited by 18
“Inflammation is an important inducer of hepcidin synthesis [18,19].”
BackgroundAndrews, M., & Olguín, M. A. (2014) · PubMed · doi:10.3305/nh.2014.30.3.7647 · Cited by 18
Lee, S. H., Jeong, S., Park, Y. S., Hwang, J., Kim, J., Kim, N., & Lee, D. H. (2010) · The Korean Journal of Hepatology · doi:10.3350/kjhep.2010.16.3.288 · Cited by 18
“In human liver cell cultures, as well as in mouse and human volunteer studies, IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation.(28) Therefore, the significantly increased serum IL-6 and prohepcidin levels seen in CH-C patients in this study support the idea that HCV infe…”
BackgroundImpact of Injury Severity on the Inflammatory State and Severe Anemia
Apple, C. G., Miller, E., Loftus, T. J., Kannan, K. B., Parvataneni, H. K., Hagen, J. E., Efron, P. A., & Mohr, A. M. (2019) · Journal of Surgical Research · doi:10.1016/j.jss.2019.10.046 · Cited by 18
Role of interleukin‐6 in hypoxic regulation of intestinal iron absorption
Raja, K. B., Latunde-Dada, G. O., Peters, T. J., McKie, A. T., & Simpson, R. J. (2005) · British Journal of Haematology · doi:10.1111/j.1365-2141.2005.05814.x · Cited by 18
“Furthermore, IL-6 has more recently been shown to rapidly and directly induce hepcidin expression in hepatocytes in both mice and humans (Nemeth et al, 2003, 2004b): Induction of inflammation in wild-type mice resulted in increased hepcidin expression and hypoferraemia, whereas IL-6 knockout mice…”
BackgroundResultInfluentialSynergistic immunotherapy targeting cancer-associated anemia: prospects of a combination strategy
Yuan, T., Jia, Q., Zhu, B., Chen, D., & Long, H. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01145-w · Cited by 20
Management of Chronic Kidney Disease
VanDeVoorde, R. G., & Warady, B. A. (2009) · Springer eBooks · doi:10.1007/978-3-540-76341-3_68 · Cited by 18
Karlsson, T. (2017) · Journal of Inflammation · doi:10.1186/s12950-017-0166-3 · Cited by 18
“IL-6 is the main positive regulator of hepcidin expression [32], but we did not find a significant difference in mean IL-6 levels between patients with ID-AI and AI and only a weak positive correlation between hepcidin and IL-6.”
Catching the complexity of salmon-louse interactions
Gallardo‐Escárate, C., Valenzuela‐Muñoz, V., Núñez-Acuña, G., Carrera, C., Gonçalves, A. T., Valenzuela‐Miranda, D., Benavente, B. P., & Roberts, S. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.04.065 · Cited by 19
Ganz, T. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-92033-2_3 · Cited by 18
Self-citationRecent Paradigm Shifts in the Diagnosis and Treatment of Rheumatoid Arthritis
Jung, Y., & Kim, H. (2012) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2012.27.4.378 · Cited by 19
“IL-6 also has pleiotropic roles in RA such as stimulating antibody production by B cells, differentiation of Th1 and Th17 cells and promoting acute phase responses and anemia [13,14].”
BackgroundIron, HCV, and Liver Cancer: Hard Metal Setting the Pace?
Mueller, S., Afdhal, N. H., & Schuppan, D. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.05.006 · Cited by 17
Han, L., Liu, Y., Lü, M., Wang, H., & Tang, F. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.022 · Cited by 17
Zhang, M., Zhao, P., Yung, W., Sheng, Y., Ke, Y., & Qian, Z. (2018) · Aging · doi:10.18632/aging.101676 · Cited by 17
“Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.”
BackgroundMethodInfluentialCoutinho, H. M., Leenstra, T., Acosta, L. P., Olveda, R. M., McGarvey, S. T., Friedman, J. F., & Kurtis, J. D. (2007) · Journal of Nutrition · doi:10.1093/jn/137.2.433 · Cited by 17
“Recent evidence suggests that IL-6 regulates hepcidin expression; this newly discovered peptide is thought to be a central regulator of iron metabolism, and may play an additional role in mediating anemia during chronic inflammation by reducing intestinal iron absorption (33,34).”
BackgroundRacial disparity in breast cancer survival: the impact of pre-treatment hematologic variables
Wang, C., Civan, J. M., Lai, Y., Cristofanilli, M., Hyslop, T., Palazzo, J., Myers, R. E., Li, B., Ye, Z., Zhang, K., et al. (2014) · Cancer Causes & Control · doi:10.1007/s10552-014-0481-4 · Cited by 17
“Chronic inflammation or chronic diseases which were more common in blacks than whites, accounted for one-third of older persons with anemia in the USA, possibly by affecting the absorption and release of iron under unfavorable physical conditions [50, 51].”
BackgroundSrivastav, A. K., Dhiman, N., Tiwari, R., Arjaria, N., Prakash, J., Jagdale, P. R., Ayanur, A., Singh, D., Patnaik, S., & Kumar, M. (2019) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2019.01.008 · Cited by 17
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
