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
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
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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 1,401–1,500 of 2,683
Moreno‐Fernández, J., Díaz‐Castro, J., Alférez, M. J. M., & López‐Aliaga, I. (2019) · Nutrients · doi:10.3390/nu11030631 · Cited by 18
“In addition, inflammatory cytokines may negatively influence Fe absorption and recycling, thereby interfering with hemoglobin synthesis [30].”
BackgroundHtet, M. K., Fahmida, U., Dillon, D., Akib, A. A., Utomo, B., & Thurnham, D. I. (2019) · Nutrients · doi:10.3390/nu11040918 · Cited by 17
“During inflammation, hepcidin is released mainly from the liver with the stimulation from pro-inflammatory cytokines especially IL-6 [7,32].”
BackgroundResistance exercise causes greater serum hepcidin elevation than endurance (cycling) exercise
Goto, K., Kojima, C., Kasai, N., Sumi, D., Hayashi, N., & Hwang, H. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228766 · Cited by 17
“First, the primary mediator for the upregulation of hepcidin secretion is believed to be IL-6 elevation [10].”
BackgroundNovel mutation in the TMPRSS 6 gene with iron‐refractory iron deficiency anemia
Kodama, K., Noguchi, A., Adachi, H., Hebiguchi, M., Yano, M., & Takahashi, T. (2014) · Pediatrics International · doi:10.1111/ped.12395 · Cited by 17
Gyarmati, B., Szabó, E., Szalay, B., Czuczy, N., Toldi, G., Cseh, Á., Vásárhelyi, B., & Takáts, Z. (2011) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2011.01586.x · Cited by 17
“intracellular signaling pathways that converge to increase hepcidin production.(2) In spite of great enthusiasm with the discovery of hepcidin in 2000,(1) methodological barriers prevent the screening of hepcidin levels under different clinical conditions.”
BackgroundFujiwara, T., Ikeda, T., Nagasaka, Y., Okitsu, Y., Katsuoka, Y., Fukuhara, N., Onishi, Y., Ishizawa, K., Ichinohasama, R., Tomosugi, N., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075568 · Cited by 17
Estrella, M. M., Astor, B. C., Köttgen, A., Selvin, E., Coresh, J., & Parekh, R. S. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq040 · Cited by 17
Treatment of Anemia in Heart Failure
Jelani, Q., & Katz, S. D. (2010) · Cardiology in Review · doi:10.1097/crd.0b013e3181e71150 · Cited by 17
“Hepcidin can also contribute to anemia of chronic disease by blocking iron release from macrophages by downregulation of ferroportin.(6,55) These changes in iron transport protein expression increase reticuloendothelial iron stores, but limit release of iron to the bone marrow for hematopoiesis.”
BackgroundHepcidin generated by hepatoma cells inhibits iron export from co-cultured THP1 monocytes
Andriopoulos, B., & Pantopoulos, K. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.10.025 · Cited by 18
“On the other hand, hepcidin is induced by iron overload [7] or by inflammatory signals via interleukins IL-1 or IL-6 [8,9].”
BackgroundPrzybyszewska, J., Żekanowska, E., Kędziora–Kornatowska, K., Boińska, J., Cichon, R., & Porzych, K. (2013) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.1623 · Cited by 17
Erythroferrone in focus: emerging perspectives in iron metabolism and hematopathologies
Babar, S., & Saboor, M. (2024) · Blood Science · doi:10.1097/bs9.0000000000000198 · Cited by 17
“4 Researchers hypothesized that erythroid progenitors might produce a factor that could suppress hepcidin, thereby increasing iron availability for erythropoiesis.”
BackgroundIron acquisition inLeishmaniaand its crucial role in infection
NIU, Q., Li, S., Chen, D., CHEN, Q., & Chen, J. (2016) · Parasitology · doi:10.1017/s0031182016000858 · Cited by 17
Iron metabolism in patients with Graves’ hyperthyroidism
Fischli, S., von Wyl, V., Trummler, M., Konrad, D., Wueest, S., Ruefer, A., Heering, K., Streuli, R., Steuer, C., Bernasconi, L., et al. (2017) · Clinical Endocrinology · doi:10.1111/cen.13450 · Cited by 18
Iron deficiency in heart failure: Efficacy and safety of intravenous iron therapy
Kang, C. K., Pope, M., Lang, C. C., & Kalra, P. R. (2017) · Cardiovascular Therapeutics · doi:10.1111/1755-5922.12301 · Cited by 17
“This may be attributed to the fact that ferritin is an acute-phase reactant which may be elevated in response to the underlying inflammatory process in CHF.([14-20]) Consequently, iron deficiency may be missed if based on serum ferritin concentration as high levels of serum ferritin may reflect inflammation rather tha…”
BackgroundInfluentialEguchi, A., Mochizuki, T., Tsukada, M., Kataoka, K., Hamaguchi, Y., Oguni, S., Nitta, K., & Tsuchiya, K. (2012) · International Journal of Nephrology · doi:10.1155/2012/239476 · Cited by 17
“Previous studies have shown markedly increased serum hepcidin levels in humans with chronic infections and severe inflammatory diseases, suggesting that elevated serum hepcidin levels play a key role in the anemia of inflammation and reticuloendothelial blockade [27].”
BackgroundSuzuki, K., Terui, Y., Nishimura, N., Mishima, Y., Sakajiri, S., Yokoyama, M., Takahashi, S., Tsuyama, N., Takeuchi, K., & Hatake, K. (2012) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hys194 · Cited by 17
“On the other hand, some inflammatory cytokines, such as IL-6 and TNF-a, are related with both anemia and CRP.”
BackgroundGao, Z., Hu, Y., Gao, Y., Ma, X., & Hu, Z. (2023) · Medicine · doi:10.1097/md.0000000000033558 · Cited by 17
“[7–11] Some studies have shown that the expression of hepcidin is regulated by inflammation and iron load.[12,13] Patients with CKD are in a chronic”
BackgroundFisher, A. L., Phillips, S., Wang, C., Paulo, J. A., Xiao, X., Xu, Y., Moschetta, G. A., Xue, Y., Mancias, J. D., & Babitt, J. L. (2024) · Blood · doi:10.1182/blood.2024024795 · Cited by 17
Zhang, J., Chen, X., Huang, D., & Tan, X. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2024.114002 · Cited by 17
Ferritinophagy and organ injury
Shao, N., Yu, H., Li, X., Han, M., Chen, C., Zhu, J., Tang, Y., Dong, J., & Chen, H. (2026) · Autophagy · doi:10.1080/15548627.2026.2633246 · Cited by 21
Scholz, G., Leichtle, A. B., Scherer, A., Arndt, U., Fiedler, M., Aeberli, D., Finckh, A., Gabay, C., Kyburz, D., Villiger, P. M., et al. (2019) · British Journal of Haematology · doi:10.1111/bjh.15895 · Cited by 17
Aloke, C., Ibiam, U. A., Obasi, N. A., Orji, O. U., Ezeani, N. N., Aja, P. M., Alum, E. U., & Mordi, J. C. (2019) · Journal of Food Biochemistry · doi:10.1111/jfbc.12912 · Cited by 17
Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice
Xiao, X., Yeoh, B. S., Saha, P., Tian, Y., Singh, V., Patterson, A. D., & Vijay-Kumar, M. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.11.014 · Cited by 16
“Hypoferremia (anemia) of inflammation is a well-known phenomenon in response to acute and chronic inflammation [11].”
BackgroundShi, Y., Zhou, L., Huang, L., Lian, Y. T., Zhang, X. M., Guo, H., Wu, T., Cheng, L., & He, M. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.05.040 · Cited by 16
Validation of a competitive ELISA assay for the quantification of human serum hepcidin.
Dahlfors, G., Stal, P. I., Hannson, E. C., Barany, P. F., Sisowath, C., Onelöv, L., Nelson, D., Eggertsen, G., Marmur, J., & Beshara, S. (2015) · PubMed · Cited by 16
Tao, H., Zhou, Y., Yin, X., Wei, X. L., & Zhou, Y. (2022) · Molecules · doi:10.3390/molecules27154903 · Cited by 16
“The known compounds (3–6) were identified on the basis of a detailed spectroscopic interpretation in comparison to the reported data in the references, to be Quercetin (3) [22], Myricetrin (4) [23], Quercitrin (5) [24], and Tamarixetin 3-O-rhamnoside (6) [25] (Figure 1).”
BackgroundHepcidin and its potential clinical utility
Miseta, A., Nagy, J., Nagy, T., Poór, V. S., Fekete, Z., & Sipos, K. (2015) · Cell Biology International · doi:10.1002/cbin.10505 · Cited by 16
“IL-6 and some other interleukins are elevated during infections and chronic inflammatory diseases (Nemeth et al., 2004; Kartikasari et al., 2008; Zhang and Rovin, 2010), and all these pathological situations were accompanied with increased hepcidin expression.”
BackgroundNovel models of cancer-related anemia in mice inoculated with IL-6-producing tumor cells
Mori, K., Fujimoto-Ouchi, K., Onuma, E., Noguchi, M., Shimonaka, Y., Yasuno, H., & Nishimura, T. (2009) · Biomedical Research · doi:10.2220/biomedres.30.47 · Cited by 16
Niihata, K., Tomosugi, N., Uehata, T., Shoji, T., Mitsumoto, K., Shimizu, M., Kawabata, H., Sakaguchi, Y., Suzuki, A., Hayashi, T., et al. (2012) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfs322 · Cited by 16
Andrews, M., Elba Leiva, M., & Arredondo, M. (2016) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2016.06.001 · Cited by 16
Unexplained Anemia in the Elderly
Ershler, W. B. (2019) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2019.03.002 · Cited by 16
Beyond tug-of-war: Iron metabolism in cooperative host–microbe interactions
Chen, G. Y., & Ayres, J. S. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008698 · Cited by 16
“Hepcidin signaling occurs in response to inflammatory signals like interleukin (IL)-6 [19] to prevent duodenal iron absorption and sequester iron within tissues and phagocytes.”
BackgroundThe role of disrupted iron homeostasis in the development and progression of arthropathy
Karim, A., Bajbouj, K., Qaisar, R., Hall, A. C., & Hamad, M. A. (2022) · Journal of Orthopaedic Research® · doi:10.1002/jor.25323 · Cited by 16
“The inflammatory response (interleukin [IL]‐1, IL‐6, toll‐like receptor [TLR]‐4 and TLR‐5, among others) has also been shown to upregulate hepcidin synthesis and thus modulate iron status.(33,34) Evidence also suggests that HFE‐dependent signals and”
BackgroundTsuboi, A., Watanabe, M., Kazumi, T., & Fukuo, K. (2013) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.16071 · Cited by 16
Is Hepcidin-25 a Clinically Relevant Parameter for the Iron Status in Hemodialysis Patients?
Brătescu, L., Bârsan, L., Munteanu, D., Stancu, S. H., & Mircescu, G. (2010) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2010.06.006 · Cited by 16
Inhibition of HCV by the serpin antithrombin III
Asmal, M., Seaman, M. S., Lin, W., Chung, R. T., Letvin, N. L., & Geiben-Lynn, R. (2012) · Virology Journal · doi:10.1186/1743-422x-9-226 · Cited by 16
“Hepcidin transcription is stimulated by iron overload as well as by inflammation through IL-6 [65], which is elevated in patients with chronic HCV.”
BackgroundSasai, M., Iso, Y., Mizukami, T., Tomosugi, N., Sambe, T., Miyazaki, A., & Suzuki, H. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.11.147 · Cited by 16
Sim, M., DAWSON, B. T., Landers, G. J., Swinkels, D. W., Wiegerinck, E. T. G., Yeap, B. B., Trinder, D., & Peeling, P. (2017) · Annals of Nutrition and Metabolism · doi:10.1159/000465530 · Cited by 16
Treatment options for anemia in the elderly
Busti, F., Marchi, G., Zidanes, A. L., Castagna, A., & Girelli, D. (2019) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2019.06.018 · Cited by 17
Díaz, R., Troncoso, J. M., Jakob, E., & Škugor, S. (2021) · BMC Veterinary Research · doi:10.1186/s12917-021-02853-6 · Cited by 17
“Hepcidin is the major iron-regulating hormone that is involved in the sequestration of iron from serum by macrophages, and is induced by proinflammatory cytokines, such as IL-1β and IL-6, activated by invading bacteria [10, 11].”
BackgroundPotential factors contributing to poor iron status with obesity
Zeid, A. A., Saka, M. H. E., Abdalfattah, A., & Zineldeen, D. H. (2013) · Alexandria Journal of Medicine · doi:10.1016/j.ajme.2013.04.007 · Cited by 16
“Obesity is chronic inflammatory condition and Hepcidin is primarily regulated by inflammatory mediators.22 IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone Hepcidin.23 IL-6 in particular has been shown to exert its effects on Hepcidin gene transcription.”
BackgroundLiver Hepcidin and Stainable Iron Expression in Biliary Atresia
Huang, Y., Yu-Hsieh, H., Huang, C., Tseng, V. S.-M., Tai, M., Chen, C., & Chuang, J. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000214974.55049.f1 · Cited by 16
Bacterial Evasion of Innate Defense at Epithelial Linings
Hornef, M. W., Normark, S. J., Henriques‐Normark, B., & Rhen, M. (2005) · KARGER eBooks · doi:10.1159/000086652 · Cited by 16
The development of erythropoietic agents in oncology
Glaspy, J. A. (2005) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.10.3.553 · Cited by 16
“Emerging Drugs (2005) 10(3) of anaemia of chronic disease was the identification of hepcidin, a Type II acute-phase polypeptide produced in response to IL-6 by the liver when chronic inflammatory illnesses such as cancer develop, and which acts on the gastrointestinal tract to decrease iron absorption and on the retic…”
BackgroundStorti, F. (2008) · Cited by 16
Tackling the unknowns in understanding and management of hospital acquired anemia
Bressman, E., Jhang, J. S., McClaskey, J. H., & Ginzburg, Y. Z. (2021) · Blood Reviews · doi:10.1016/j.blre.2021.100830 · Cited by 18
Increased Risk of Anemia in Patients with Asthma
Rhew, K., Choi, J., Kim, K., Choi, K. H., Lee, S.-H., & Park, H. (2023) · Clinical Epidemiology · doi:10.2147/clep.s394717 · Cited by 16
“Eventually, prolonged immune activation will lead to functional iron deficiency32 and, over time, will develop into ACD.33 The study by Shaheen reported that these direct links between asthma and iron deficiency are apparent.34 Anemia is an important risk factor for cardiovascular disease and mortality.35,36 Especiall…”
BackgroundInfluentialMohapatra, A., Dixit, A., Garg, L. C., & Sahoo, P. K. (2019) · Aquaculture · doi:10.1016/j.aquaculture.2019.734218 · Cited by 16
van der Staaij, H., Donker, A. E., Bakkeren, D. L., Salemans, J. M. J. I., Mignot-Evers, L. A. A., Bongers, M. Y., Dieleman, J. P., Galesloot, T. E., Laarakkers, C. M., Klaver, S. M., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031917 · Cited by 16
Iron as a Therapeutic Target in HFE-Related Hemochromatosis: Usual and Novel Aspects
Loréal, O., Cavey, T., Robin, F., Kenawi, M., Guggenbuhl, P., & Brissot, P. (2018) · Pharmaceuticals · doi:10.3390/ph11040131 · Cited by 17
“Hepcidin expression is regulated by many factors, including iron status [19] and inflammation [19,22] that induce an upregulation of hepcidin expression, and hypoxia/erythropoiesis activity [23–25] that decrease hepcidin expression.”
BackgroundIron and Atherosclerosis: Nailing Down a Novel Target with Magnetic Resonance
Sharkey‐Toppen, T., Tewari, A. K., & Raman, S. V. (2014) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-014-9551-y · Cited by 16
“During iron loading and inflammation, hepcidin is stimulated by an iron feedback mechanism [3, 38, 39].”
Cardiac injury caused by iron overload in thalassemia
Fu, C., & Yang, X. Y. (2025) · Frontiers in Pediatrics · doi:10.3389/fped.2025.1514722 · Cited by 16
Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis
Sharma, R., Zhao, W., Zafar, Y., Murali, A. R., & Brown, K. E. (2023) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2023-0540 · Cited by 16
Up-regulation of CD64 Expression on Monocytes in Patients With Active Adult-Onset Still Disease
Shimizu, T., Kikuchi‐Taura, A., Tsuji, S., Matsushita, M., Ohshima, S., & Saeki, Y. (2018) · JCR Journal of Clinical Rheumatology · doi:10.1097/rhu.0000000000000931 · Cited by 15
Isocitrate treatment of acute anemia of inflammation in a mouse model
Kim, A., Fung, E., Parikh, S. G., Gabayan, V. R., Nemeth, E., & Ganz, T. (2015) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2015.09.007 · Cited by 15
“During inflammation or infection, hepcidin expression is strongly stimulated, largely by IL-6 [7] via the JAK-STAT pathway [8–10].”
BackgroundInfluentialSelf-citationLayoun, A., Samba-Mondonga, M., Fragoso, G., Calvé, A., & Santos, M. M. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00159 · Cited by 15
“Two major pathways that contribute to hepcidin regulation are the inflammatory pathway mediated through IL-6/STAT3 signaling (Nemeth et al., 2004; Verga Falzacappa et al., 2007), and the iron-sensing pathway, which is mediated through BMP/SMAD signaling (Rishi et al.”
BackgroundHal, A. M., & El‐Barbary, M. I. (2020) · Aquaculture · doi:10.1016/j.aquaculture.2020.736071 · Cited by 15
Iron and Ferritin Levels in the Serum and Milk of Bovine Leukemia Virus-Infected Dairy Cows
Schnell, S. A., OHTSUKA, H., Kakinuma, S., Yoshikawa, Y., Watanabe, K., & Orino, K. (2015) · Frontiers in Veterinary Science · doi:10.3389/fvets.2015.00012 · Cited by 15
“Additionally, serum iron levels are decreased in animals suffering from inflammatory diseases, an effect that results from IL-6 mediated hypoferremia (20).”
BackgroundChanges in serum hepcidin levels in acute iron intoxication in a rat model
Ben–Assa, E., Youngster, I., Kozer, E., Abu‐Kishk, I., Bar-Haim, A., Bar‐Oz, B., & Berkovitch, M. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.06.848 · Cited by 15
Sellam, J., Kotti, S., Fellahi, S., Bastard, J., Meyer, M., Lioté, F., Meyer, O., Simon, T., Capeau, J., & Berenbaum, F. (2012) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2012-202119 · Cited by 15
“Hepcidin is an interleukin-6 induced peptide hormone involved in iron metabolism and inflammation.(1) Serum hepcidin level may distinguish anaemia due to chronic inflammation and/or iron deficiency in rheumatoid arthritis (RA) patients.”
BackgroundHematological and Biochemical Markers of Iron Status in a Male, Young, Physically Active Population
Nunes, L. A. S., Grotto, H. Z. W., Brenzikofer, R., & de Macedo, D. V. (2014) · BioMed Research International · doi:10.1155/2014/349182 · Cited by 15
“Hepcidin levels increase 3–24 hours after exercise in response to IL-6, producing rapid decreases in the plasma iron concentration [40, 41].”
BackgroundGirndt, M., Stenvinkel, P., Ulrich, C., Axelsson, J., Nordfors, L., Barany, P. F., Carrero, J. J., Heine, G. H., Kaul, H., & Kohler, H. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm244 · Cited by 15
“IL-6 induces the hepatic synthesis of the proteins hepcidin and ferritin [26].”
BackgroundChange in iron metabolism in rats after renal ischemia/reperfusion injury
Xie, G.-L., Zhu, L., Zhang, Y., Zhang, Q.-N., & Yu, Q. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175945 · Cited by 15
TSUKANO, K., Shimamori, T., Fukuda, T., Nishi, Y., OTSUKA, M., Kitade, Y., & Suzuki, K. (2019) · Journal of Veterinary Medical Science · doi:10.1292/jvms.19-0002 · Cited by 15
“IL-6 infusion in humans induces hepcidin excretion and a decrease in serum iron [15].”
BackgroundAnemia and its impact on function in nursing home residents: What do we know?
Sabol, V. K., Resnick, B. M., Galik, E. M., Gruber‐Baldini, A. L., Morton, P. G., & Hicks, G. E. (2010) · Journal of the American Academy of Nurse Practitioners · doi:10.1111/j.1745-7599.2009.00471.x · Cited by 15
“…anemia on function in NH residents glycoprotein synthesized in the liver that is stimulated by the presence of inflammatory cytokine interleukin-6 (IL-6), may impair duodenal absorption of iron and release of recycled iron from macrophages (Andrews, 2004; Ferucci et al., 2005; Nemeth et al., 2004).”
BackgroundGarrido, P., Ribeiro, S., Fernandes, J. C., Vala, H., Rocha‐Pereira, P., Bronze-da-Rocha, E., Belo, L., Costa, E. M., Santos‐Silva, A., & Reis, F. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms17010028 · Cited by 15
“A disturbance in iron homeostasis is also a hallmark of the anemia of CKD, which usually presents as a functional iron deficient anemia, with low serum iron and transferrin alongside with normal or even high ferritin [30] explained by the underlying inflammatory process in CKD patients, presenting increased hepcidin l…”
BackgroundDiago, C. A. A., García‐Unzueta, M. T., Fariñas, M. C., & Amado, J. (2015) · Endocrinología y Nutrición · doi:10.1016/j.endonu.2015.09.005 · Cited by 15
Calcitriol-modulated human antibiotics: New pathophysiological aspects of vitamin D
Diago, C. A. A., García‐Unzueta, M. T., Fariñas, M. C., & Amado, J. (2016) · Endocrinología y Nutrición (English Edition) · doi:10.1016/j.endoen.2016.02.003 · Cited by 15
Gene alteration in zebrafish exposed to a mixture of substances of abuse
Subedi, B., Anderson, S., Croft, T., Rouchka, E. C., Zhang, M., & Hammond-Weinberger, D. R. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.116777 · Cited by 15
Jackaman, C., Gardner, J. K., Tomay, F., Spowart, J., Radley‐Crabb, H. G., Dye, D. E., Fox, S. A., Proksch, S., Metharom, P., Dhaliwal, S. S., et al. (2019) · OncoImmunology · doi:10.1080/2162402x.2018.1564452 · Cited by 15
“Increased inflammatory cytokines may induce liver and kidney damage, for example elevated IL-6 is associated with iron accumulation leading to oxidative tissue damage.(25) Therefore, we also looked for evidence of age-related changes to liver and kidney function.”
BackgroundJones, A. D., Shi, Z., Lambrecht, N., Jiang, Y., Wang, J., Burmeister, M., Ming, L., & Lozoff, B. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab133 · Cited by 16
Tarancón‐Díez, L., Iriarte‐Gahete, M., Sanchez-Mingo, P., Muñoz‐Fernández, M. Á., Navarro‐Gómez, M. L., Pacheco, Y. M., & Leal, M. (2025) · Scientific Reports · doi:10.1038/s41598-024-84498-7 · Cited by 15
“Hepcidin reduces iron export to plasma by decreasing intestinal absorption by acting as an inhibitor of the iron transporter ferroportin 1 in the duodenum and also diminishes iron release from erythrocyte-recycling macrophages 9 .”
Banerjee, S., & Datta, R. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105064 · Cited by 15
Swellam, M., Gabal, K. M. A., & Youssef, S. S. (2013) · IUBMB Life · doi:10.1002/iub.1205 · Cited by 14
“Production of hepcidin is regulated by interleukin-6 (IL-6) (8,9).”
BackgroundPotential hazards of recent trends in liberal iron use for renal anemia
Nakanishi, T., & Kuragano, T. (2020) · Clinical Kidney Journal · doi:10.1093/ckj/sfaa117 · Cited by 14
Sertçakacılar, G., & Yıldız, G. Ö. (2022) · Clinics and Practice · doi:10.3390/clinpract12040057 · Cited by 14
“As a result of the stimulation of hepcidin by proinflammatory cytokines and, most notably, interleukin (IL)-6 [18,19], anemia occurs because iron is retained in the cells, and its flow into the plasma decreases [20].”
BackgroundInterpreting Iron Homeostasis in Congenital and Acquired Disorders
Scaramellini, N., Fischer, D. P., Agarvas, A. R., Motta, I., Muckenthaler, M. U., & Mertens, C. (2023) · Pharmaceuticals · doi:10.3390/ph16030329 · Cited by 14
“In contrast to iron-mediated regulation of hepcidin via the BMP-SMAD pathway, inflammation-mediated regulation occurs via the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways [43].”
BackgroundToblli, J. E., Cao, G., & Angerosa, M. (2015) · BioMetals · doi:10.1007/s10534-015-9822-3 · Cited by 14
“Highly increased IL-6 levels in ISS-treated animals may also have contributed to the increase in cellular iron levels via inducing the expression of hepcidin (Nemeth et al. 2004a), which reduces the iron transport via ferroportin (Nemeth et al. 2004b).”
Backgroundde Oliveira, A. L. G., Chaves, A. T., Menezes, C. A. D. S., Guimarães, N. S., Bueno, L. L., Fujiwara, R. T., & Rocha, M. O. D. C. (2017) · Microbes and Infection · doi:10.1016/j.micinf.2017.03.001 · Cited by 14
Discovery of DS79182026: A potent orally active hepcidin production inhibitor
Fukuda, T., Goto, R., Kiho, T., Ueda, K., Muramatsu, S., Hashimoto, M., Aki, A., Watanabe, K., & Tanaka, N. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.07.004 · Cited by 14
Lorenz, L., Peter, A., Arand, J., Springer, L., Poets, C. F., & Franz, A. R. (2017) · Neonatology · doi:10.1159/000477124 · Cited by 14
Feldman, T. P., & Egan, E. S. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.917267 · Cited by 14
Abosalif, K. O. A., Abdalla, A. E., Junaid, K., Eltayeb, L. B., & Ejaz, H. (2023) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2023.103805 · Cited by 14
Sánchez‐González, C., Rivas‐García, L., López-Chaves, C., Rodríguez‐Nogales, A., Algieri, F., Gálvez, J., Gómez-Aracena, J., Ramírez, L. V., Montes‐Bayón, M., Sanz‐Medel, A., et al. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.08.011 · Cited by 14
“Levels of IL-6, TNF-a and ferritin in serum and of iron in the liver, spleen and heart increased.”
BackgroundInfluentialHepatic Hepcidin Gene Expression in Dogs with a Congenital Portosystemic Shunt
Frowde, P. E., Gow, A. G., Burton, C. A., Powell, R. M., Lipscomb, V. J., House, A. K., Mellanby, R. J., & Tivers, M. (2014) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.12387 · Cited by 14
“Increased hepcidin expression, induced by sustained up-regulation of IL-6 during chronic inflammation, has been proposed as the main mediator of anemia of chronic disease because of iron-restricted erythropoiesis.(7,8) This observation is particularly relevant to dogs with a cPSS because IL-6 concentrations are increa…”
BackgroundBrickley, E. B., Spottiswoode, N., Kabyemela, E., Morrison, R., Kurtis, J. D., Wood, A., Drakesmith, H., Fried, M., & Duffy, P. E. (2016) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.16-0218 · Cited by 14
“37 With the exception of tumor necrosis factor receptor II and interleukin 5, log e hepcidin levels had continuous, approximately linear positive associations with the inflammatory mediators, which were highly consistent across the cord, maternal peripheral, and placental blood samples.”
BackgroundThe effect of nonsurgical periodontal therapy on hepcidin and on inflammatory and iron marker levels
Leite, S. A. M., Casanovas, R. C., Rodrigues, V. P., Pereira, A. D. F. V., Ferreira, T. C. A., do Nascimento, F. R. F., do Nascimento, J. R., Gomes‐Filho, I. S., Bastos, M. G., & Pereira, A. L. A. (2019) · Brazilian Oral Research · doi:10.1590/1807-3107bor-2019.vol33.0055 · Cited by 14
Huang, Y., Huang, C., Chuang, J., Cs, H., Lee, S.-Y., & Chen, C. (2008) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2008.03.037 · Cited by 14
“Moreover, hepcidin, a gene that is upregulated in the liver by inflammation and iron overload, is a negative regulator of iron absorption from the duodenum and is released from macrophages [9-12].”
BackgroundHepcidin and multiple myeloma related anemia
Cucuianu, A., Paţiu, M., & Rusu, A. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.08.041 · Cited by 14
“Recent studies have demonstrated that a key pathophysiological role in ACD is played by hepcidin, a peptidic hormone produced in the liver, under the stimulus of inflammatory cytokines, especially IL-6 [9].”
BackgroundAndrews, M., & Arredondo, M. (2012) · BioMetals · doi:10.1007/s10534-012-9543-9 · Cited by 14
“In vitro stimulation of fresh human hepatocytes with IL-6 induces strong expression of hepcidin mRNA, and hepcidin synthesis by hepatocytes is transcriptionally regulated by IL-6 (Nemeth et al. 2004; Nemeth et al. 2003).”
BackgroundLaboratory Testing in Pediatric Rheumatology
Mehta, J. (2012) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2012.03.008 · Cited by 14
Iron‐related markers are associated with infection after liver transplantation
Chow, J. K. L., Ganz, T., Ruthazer, R., Simpson, M. A., Pomfret, E. A., Gordon, F. D., Westerman, M. E., & Snydman, D. R. (2017) · Liver Transplantation · doi:10.1002/lt.24817 · Cited by 14
“Cumulative RBC units 12 (6-20) 13 (8-24) 9 (4-17) 0.”
BackgroundResultInfluentialSelf-citationSerum Pro‐hepcidin as an Indicator of Iron Status in Dialysis Patients
Tsuchihashi, D., Abe, T., Komaba, H., Fujii, H., Hamada, Y., Nii‐Kono, T., Tanaka, M., & Fukagawa, M. (2008) · Therapeutic Apheresis and Dialysis · doi:10.1111/j.1744-9987.2008.00578.x · Cited by 14
Iron Deficiency and Iron Deficiency Anaemia in Infants Aged 9 to 12 Months in Estonia
Vendt, N. (2008) · DSpace repository (University of Tartu) · Cited by 14
The tendency of anemia of inflammation in periodontal diseases
Han, Y., Luo, Z., Yue, Z., Li, M., Xv, M., Chang, S. H., Zhan, Y., & Hou, J. (2023) · Clinical Science · doi:10.1042/cs20220524 · Cited by 14
Heidarpour, M., Mohri, M., Fallah-Rad, A. H., Shahreza, F. D., & Mohammadi, M. (2012) · Comparative Clinical Pathology · doi:10.1007/s00580-012-1576-5 · Cited by 14
“These cytokines play a central role in increasing hepcidin which inhibits both absorption of dietary iron from intestinal epithelium and export of iron from macrophages and hepatocytes (Nemeth et al. 2004).”
BackgroundNew concepts in iron deficiency anaemia
Keshav, S., & Stevens, R. (2016) · British Journal of General Practice · doi:10.3399/bjgp17x688465 · Cited by 14
Kringel, D., Lippmann, C., Parnham, M. J., Kalso, E. A., Ultsch, A., & Lötsch, J. (2018) · European Journal of Pain · doi:10.1002/ejp.1270 · Cited by 14
“This subset included interleukin ( IL-1B , IL-4 , IL-6 , IL-10 ) (Dinarello, 1994; Choi and Reiser, 1998; Mocellin et al., 2004; Nemeth et al., 2004), interleukin receptor ( IL-1RN , IL-4R ) (Bittar and Bit-tar, 1996) and histocompatibility complex-related ( HLA-B ) genes (Dupont and Ceppellini,…”
Chen, S., Ni, Y., Li, C.-C., & Liu, S. (2018) · Pediatrics & Neonatology · doi:10.1016/j.pedneo.2018.02.007 · Cited by 14
Elsheemy, M. S. A.-E., Hasanin, A. H., Mansour, A., Mehrez, S. I., & Abdelbary, M. S. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108740 · Cited by 14
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
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