The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; 11 of the 30 sources its claims cite were checked for support.
IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin
Open accessAbstract
Hypoferremia is a common response to systemic infections or generalized inflammatory disorders.In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown.Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6-hepcidin axis is responsible for the hypoferremia of inflammation. Methods Macrophage culture.Monocytes from peripheral blood were isolated by centrifugation through Ficoll-Paque (Amersham Pharmacia Biotech, Piscataway, New Jersey, USA) and 46% iso-Nonstandard abbreviations used: anemia of inflammation (AI); Iscove's modified Dulbecco's medium (IMDM); medium from LPS-stimulated macrophages (M-LPS); medium from unstimulated macrophages (M); recombinant human IL-6 (rhIL-6); total iron-binding capacity (TIBC); unsaturated iron-binding capacity (UIBC). Conflict of interest:The authors have declared that no conflict of interest exists.
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Claims the paper makes
11 of 30 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“patients with AI due to inflammatory disorders or infections had markedly increased excretion of urinary hepcidin”
What the sources say
- Supportedcites [12] source
The Results and discussion report elevated urinary hepcidin excretion in patients diagnosed with anemia of inflammation compared with healthy subjects and other patient groups. The same section reports very high excretion in a patient with epididymitis and sepsis, supporting the infection component of the claim. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“decreased serum iron”
What the sources say
- Supportedcites [8] Nicolas, 2002, J. Clin. Invest. source
The Results section reports a twofold decrease in serum iron in wild-type mice 16 hours after turpentine injection (Figure 6a). It also notes that this decrease was not observed in hepcidin-deficient mice. (LLM, conf=0.95)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“injections of turpentine increased hepcidin mRNA”
What the sources say
- Supportedcites [8] Nicolas, 2002, J. Clin. Invest. source
The Results section reports a sixfold increase in liver hepcidin gene expression 16 hours after turpentine injection compared with saline-injected controls. The discussion (p. 1042) explicitly describes this as a sixfold increase in liver hepcidin mRNA in mice. (LLM, conf=0.95)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“strong induction of hepcidin mRNA by IL-6”
What the sources say
- Supportedcites [12] source
The Results and discussion section reports that IL-6 induced hepcidin in primary human hepatocytes within 8 hours, with a 25-fold increase. The Figure 2 caption identifies the measured signal as hepcidin mRNA. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“but not IL-1 α or TNFα”
What the sources say
- Supportedcites [12] source
The Results and discussion section reports that IL-1α and TNF-α did not induce hepcidin mRNA within eight hours in primary human hepatocytes, unlike IL-6. It also notes that IL-1α induced hepcidin mRNA after 24 hours, probably indirectly through IL-6; the claim is consistent with the lack of strong direct induction. (LLM, conf=0.90)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LPS treatment increased hepcidin mRNA levels in primary human hepatocytes”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Anti-TNFα Ab's had no detectable effect in either experiment”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hep3B hepcidin mRNA, however, markedly increased after exposure to M-LPS”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Anti-IL-6 Ab's had similar inhibitory effects when hepatocytes or Hep3B cells were treated with conditioned medium from macrophages exposed to peptidoglycan from Staphylococcus aureus”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in IL-6 KO mice hepcidin mRNA increased ninefold”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 10
- It may state two separate claims as one. 17
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“hepcidin synthesis is regulated by dietary iron and iron stores, as well as by tissue oxygenation”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
Section 3.4 reports increased liver HEPC1 and HEPC2 transcripts in mice given dietary carbonyl iron or injected iron–dextran, supporting regulation by iron excess. The paper does not establish regulation by iron stores specifically, and no passage addresses tissue oxygenation; it measures gene expression rather than hepcidin synthesis directly. (LLM, conf=0.88)
- Partly supportedcites [8] Nicolas, 2002, J. Clin. Invest. sourceExperimental — accuracy not yet measured
The hypoxia results report that reduced tissue oxygenation downregulated hepcidin gene expression in mice. The anemia results show that iron loading increased expression, and the Discussion links iron deficiency to low expression until stores are repleted. The paper does not show that dietary iron itself regulates hepcidin synthesis; it describes hepcidin regulating dietary iron absorption instead. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the turpentine-induced hypoferremia was not observed in hepcidin-deficient mice (8), demonstrating that hepcidin is required for iron sequestration during inflammatory conditions”
What the sources say
- Partly supportedcites [8] Nicolas, 2002, J. Clin. Invest. sourceExperimental — accuracy not yet measured
The results and discussion (p. 1042) report that turpentine lowered serum iron in wild-type mice but not in hepcidin-deficient mice. They establish hepcidin’s role in the inflammatory fall in serum iron, but describe iron sequestration as a proposed mechanism, not one directly demonstrated by that experiment. (LLM, conf=0.84)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“hepcidin mRNA expression was increased in mice with dietinduced or genetically induced iron overload”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
Section 3.4 reports increased liver HEPC1 and HEPC2 transcripts in mice given dietary carbonyl iron, supporting the diet-induced part. The paper does not report increased hepcidin mRNA in genetically iron-overloaded mice; its Introduction instead describes iron overload in USF2 knockout mice that lack hepcidin transcripts. Page numbers are not available in our copy. (LLM, conf=0.87)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“decreased in mice with anemia caused by bleeding or hemolysis or in mice with hypoxemia due to decreased ambient oxygen”
What the sources say
- Supportedcites [8] Nicolas, 2002, J. Clin. Invest. source
In “Hepcidin gene expression is decreased after experimentally induced anemia,” the paper reports reduced liver hepcidin mRNA after bleeding and reduced hepcidin expression after PHZ-induced hemolytic anemia. In “Hepcidin gene expression is tightly controlled by hypoxia,” it reports downregulation in mice exposed to reduced oxygen pressure in a hypobaric chamber. The hypoxic reduction was clear after two and four days, though results varied after twelve days. (LLM, conf=0.93)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“in the most common form of hemochromatosis, that caused by mutations in the HFE gene”
What the sources say
- Not checked — no full text of the sourcecites [11] source
- Could not verifycites [12] sourceExperimental — accuracy not yet measured
The Results and discussion (page unavailable) compare urinary hepcidin in patients with well-controlled hereditary hemochromatosis with levels in patients with anemia of inflammation, but do not say hepcidin production is diminished relative to healthy people. A search for HFE mutations found no passage identifying the hemochromatosis patients as having HFE-related disease. (LLM, conf=0.76)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-6 infusion rapidly increased hepcidin excretion (Figure 4B); within 2 hours after the infusion, urinary hepcidin levels were 7.5-fold higher on average than at 0 hours”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“serum iron decreased on average 34% and transferrin saturation decreased 33% in comparison to preinfusion values”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TNFα markedly suppressed hepcidin mRNA levels by a mechanism that did not involve IL-6 regulation”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“both the effects of LPS on primary human hepatocytes and the effects of M-LPS on Hep3B cells were completely reversed when IL-6-neutralizing Ab's were added”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“median haptoglobin mRNA was 9.3-fold higher in turpentine-treated WT mice but only 1.9-fold higher in IL-6 KO mice”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inflammatory and iron pathways of hepcidin stimulation respond rapidly, with major hepcidin increase detectable within 1 day in both humans and mice”
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“hepcidin mRNA was increased in the livers of LPS-treated mice and in LPS-treated hepatocytes”
What the sources say
- Not checked — no full text of the sourcecites [3] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“There is a single human hepcidin gene whose essential role in iron homeostasis was confirmed by identifying homozygous frameshift or nonsense mutations in affected individuals with severe juvenile hemochromatosis”
What the sources say
- Not checked — no full text of the sourcecites [9] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“in transgenic mice overexpressing hepcidin-1 (4), transplacental and intestinal iron transport was blocked, and the mice died at birth from severe iron deficiency unless given parenteral iron supplementation”
What the sources say
- Not checked — no full text of the sourcecites [4] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations suggest that human hepcidin is the functional equivalent of hepcidin-1 in mice.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Overexpression of the other known murine hepcidin gene, hepcidin-2, had no effect on iron metabolism in mice”
What the sources say
- Not checked — no full text of the sourcecites [6] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Hepcidin production was also diminished in another form of juvenile hemochromatosis due to mutations in the hemojuvelin gene”
What the sources say
- Not checked — no full text of the sourcecites [10] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Hepatic hepcidin mRNA levels in mice were shown to increase in response to increased dietary iron”
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In IL-6 KO mice, however, hepcidin mRNA was suppressed, likely due to the negative regulation of hepcidin synthesis by other acute-phase cytokines”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“changes in serum iron concentrations reflected the pattern of hepcidin induction: turpentine treatment caused serum iron decrease in WT mice, but no change in iron levels was detected in IL-6 KO mice”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the decrease in iron supply becomes a bottleneck for hemoglobin synthesis and eventually results in anemia”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When the rate of iron release from macrophages drops, plasma iron concentrations rapidly decrease”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there are at least three major and distinct pathways of regulation of hepcidin: regulation by inflammation, dependent on IL-6; regulation by iron, dependent on some other factor, perhaps transferrin saturation; and suppression of hepcidin production during hypoxia and anemia”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“transgenic overexpression of IL-6 in mice (36) and repeated administration of IL-6 in rats and cancer patients (33) has been reported to cause anemia”
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
IL-6 KO mice do not produce functional IL-6.
“Two pairs of IL-6 -/- (IL-6 KO) mice on a C57BL/6 background”
The paper relies on this without support.
Hepatic hepcidin mRNA levels reflect hepcidin synthesis or activity.
“Median hepcidin-1 expression in the liver increased 12-fold”
The paper relies on this without support.
Turpentine-induced inflammation in mice is a valid model of human inflammatory hypoferremia.
“we used the turpentine-induced mouse model of inflammation”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“increased concentrations of hepcidin then inhibit ferroportin activity”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [52]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“leading to depletion of iron in plasma and extracellular fluid (hypoferremia).”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [52]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As a consequence of this interaction, the absorption of iron from the diet is reduced due to hepcidin mediated reduction of ferroportin expression in enterocytes, thereby resulting in a reduction of circulating iron levels which is further aggravated by the inhibition of iron export from macrophages by the same mechanism (Nemeth et al., 2004a; Kemna et al., 2005; Roy et al., 2007; Theurl et al., 2”
From Iron at the interface of immunity and infection (2014) · cites this paper as Nemeth et al., 2004a
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Infection and inflammation induce hepcidin, predominantly through the effects of the cytokine interleukin-6 (IL-6) [52]”
From Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis (2021) · cites this paper as [52]
The cited source says what the claim attributes to it.
In the citing paper
“Blockade of IL-6 receptor signaling prevented the hepatocyte-derived generation of hepcidin, which interferes with iron absorption (Nemeth et al., 2004”
From Targeting Interleukin-6 Signaling in Clinic (2019) · cites this paper as Nemeth et al., 2004
In the citing paper
“Interleukin-6 (IL-6) is the main cytokine that stimulates hepcidin synthesis during infection19 and inflammation, but other factors can also contribute, including activin B20, type I interferons (IFNs)21,22 and BMP2 (REF. 23).”
From Iron homeostasis in host defence and inflammation (2015) · cites this paper as [19]
In the citing paper
“Proinflammatory cytokines induced by inflammation can stimulate anemia of inflammation by limiting serum iron and increasing cellular iron stores by modulating the expression and activity of various iron regulatory proteins including hepcidin, FPN, ferritin, and the iron importer divalent metal transporter 1 (DMT1) [25–30].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [25]
In the citing paper
“However, hepcidin is overexpressed in inflammatory disease and is an early inflammatory marker [245,341-345].”
In the citing paper
“during an inflammatory episode interleukin-6 (IL-6) signals to the liver to release the hormone hepcidin, which promotes iron accumulation in phagocytic cells by inducing degradation of the iron exporter ferroportin (Fpn1) (Nemeth et al., 2004).”
From The Impact of Dietary Transition Metals on Host-Bacterial Interactions (2018) · cites this paper as Nemeth et al., 2004
In the citing paper
“The inflammatory increase in hepcidin is mainly caused by increased concentrations of IL-6 (interleukin-6) [19], inducing the transcription of the hepcidin gene through the JAK2/STAT3 [20][21][22] pathway.”
From Iron and infection (2018) · cites this paper as [19]
In the citing paper
“The role of IL-6 is important in many models of infection and inflammation [19,24] but in some models other cytokines may partially replace its stimulatory effect on hepcidin [17].”
From Iron and infection (2018) · cites this paper as [19]
In the citing paper
“One main contributing factor to pathologic iron homeostasis is interleukin (IL)-6 mediated induction of hepcidin expression through the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway [154].”
From Iron in immune cell function and host defense (2021) · cites this paper as [154]
In the citing paper
“During inflammation, HAMP is induced in hepatocytes alongside a battery of other acute‐phase proteins, downstream of interleukin‐6 and toll‐like receptor signalling‐associated pathways. 98”
From The battle for iron in enteric infections (2020) · cites this paper as [98]
In the citing paper
“To correct this, all animals were conditioned on a low-iron diet (2-4 ppm iron; Teklad diet TD.80396, Envigo) for 5-7 days prior to, and throughout the duration of, all experiments.”
From Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia (2017) · cites this paper as [43]
In the citing paper
“Accordingly, IL6 is a key mediator of inflammation-driven iron handling, as it induces the production of hepcidin, the master regulator of iron homeostasis [4].”
In the citing paper
“It has been suggested that the COVID-19 related inflammation may be the main cause of COVID-19 associated iron disorders, as an inflammation-driven dysregulation of iron homeostasis is well established [4, 6, 7].”
In the citing paper
“The study of hepcidin regulation in mice housed under standard conditions is confounded by the high iron content of most commercial mouse chow blends.”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [16]
In the citing paper
“Sustained elevation of hepcidin expression, as occurs in many inflammatory states, results in anemia due to reduced availability of iron for erythropoiesis, a condition previously known as “anemia of chronic disease” and more accurately renamed as “anemia of inflammation” [16,22,23].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [16]
In the citing paper
“In animal models, diverse inflammatory and infectious stimuli, including Streptococcus species, Pseudomonas aeruginosa, Aspergillus fumigatus, influenza, turpentine, and lipopolysaccharide (LPS) robustly induce hepcidin in the liver via the induction of IL-6, resulting in rapid reduction in serum iron levels [16,19–21].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [16]
In the citing paper
“In the context of inflammation, IL-6 and IL-22 stimulate HAMP expression via specific receptors signaling through signal transducer and activator of transcription (STAT)-3, while alpha-1 antitrypsin may do so via HJV and matriptase-2 [69–71].”
From Iron deficiency or anemia of inflammation?: Differential diagnosis and mechanisms of anemia of inflammation (2016) · cites this paper as [70]
In the citing paper
“but is also an acute phase protein upregulated by inflammatory cytokines, notably IL-6 [18–20].”
From Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans (2015) · cites this paper as [19]
In the citing paper
“During neuroinflammation, glial cells are activated, which perturbs iron homoeostasis.34,35”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [35]
In the citing paper
“Serum sTR concentration reflects total erythroid activity and iron status and has been shown to reflect plasma iron turnover and erythroid transferrin uptake if iron deficiency is not present (22,25).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [22]
In the citing paper
“Serum sTR concentration reflects total erythroid activity in rats and humans and has been shown to reflect plasma iron turnover and erythroid transferrin uptake very closely if iron deficiency is not present (22).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [22]
In the citing paper
“We found that the hepatocytelike cells of the adenomas expressed very high levels of hepcidin 100 and speculated that our results could be generalized-that induction of hepcidin expression in response to inflammation might explain the anemia of chronic disease.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [197]
In the citing paper
“In mice, HFE2 is localized to the surface of periportal hepatocytes, and HFE2-mutant mice display iron loading and a striking decrease in hepcidin upregulation in response to increased iron from exogenous sources, compared with controls (217).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [217]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Human iron-supplementation participant count differs
MinorThe Methods section says six volunteers participated in the iron-supplementation study, while the Results section says five subjects took the iron supplements.
“Six healthy volunteers collected first morning urine for 9 days.”
“Five subjects took 65 mg of iron (as ferrous sulfate) for 3 days, and their urinary hepcidin was monitored before, during, and after iron supplementation.”
Citations
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Hepcidin, a urinary antimicrobial peptide synthesized in the liver
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Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
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Self-citationHepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
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Self-citationLEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity
Krause, A., Neitz, S., Mägert, H.-J., Schulz, A., Forssmann, W.-G., Schulz-Knappe, P., & Adermann, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01920-7 · Cited by 1,324
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282
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Items 1,501–1,600 of 2,683
Wei, S., Liu, W., Qi, Y., Guo, Y., Zhang, S., Wang, L., Zhuang, T., Zhang, N., & Liu, S. (2020) · British Journal of Haematology · doi:10.1111/bjh.17049 · Cited by 14
“IL-6 is a potent regulator upregulating hepcidin transcription via the JAK-STAT3 pathway under inflammation.(34,40) However, in this study, we did not observe significant induction of serum IL-6 in women with spontaneous abortion relative to non-pregnant and healthy pregnant women (Fig S1), excluding the contribution…”
BackgroundPrevalence of Anemia in Pediatric Patients According to Asthma Control: Propensity Score Analysis
Chang, J., Lee, H., Kim, J., & Rhew, K. (2021) · Journal of Asthma and Allergy · doi:10.2147/jaa.s318641 · Cited by 14
“IL-6 was shown to stimulate the production of hepcidin by hepatocytes, which interferes with iron homeostasis.(41,42) However, there are limitations in applying this potential role of inflammatory cytokines to pediatric population since pediatric diseases develop during maturation of tissues (ie lung) and immune syste…”
BackgroundHepcidin and the anemia of chronic disease.
Haurani, F. I. (2006) · PubMed · Cited by 14
Alshuweishi, Y., Alfaifi, M. A., Almoghrabi, Y. M., Al‐Sheikh, Y. A., & Alfhili, M. A. (2023) · Medicina · doi:10.3390/medicina59091592 · Cited by 14
“Hepcidin expression is upregulated by inflammation and it has also been shown that interleukin-6 enhances the hepatic synthesis of hepcidin, which regulates iron recycling, leading to the development of anemia due to hypoferremia [40].”
BackgroundThe potential role of ferroptosis in COVID-19-related cardiovascular injury
Yang, L., Wu, Y., Jin, W., Mo, N., Ye, G., Su, Z., Tang, L., Wang, Y., Li, Y., & Du, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115637 · Cited by 15
Oxidative battles in tuberculosis: walking the ferroptotic tightrope
Araújo‐Pereira, M., & Andrade, B. B. (2025) · Trends in Immunology · doi:10.1016/j.it.2025.02.009 · Cited by 16
Zhu, J., Fu, Q., Wang, S., Ren, L., Feng, W., Wei, S., Zhang, Z., Xu, Y. H., Ganz, T., & Liu, S. (2022) · Nano Letters · doi:10.1021/acs.nanolett.1c04260 · Cited by 14
Self-citationBalounová, J., Vavrochová, T., Benešová, M., Ballek, O., Kolář, M., & Filipp, D. (2014) · European Journal of Immunology · doi:10.1002/eji.201344040 · Cited by 13
Hepcidin levels and gastric cancer risk in the EPIC‐EurGast study
Jakszyn, P. G., Fonseca‐Nunes, A., Luján‐Barroso, L., Aranda, N., Tous, M., Arija, V., Cross, A. J., Bueno-de-Mesquita, H. B., Weiderpass, E., Kuhn, T. E., et al. (2017) · International Journal of Cancer · doi:10.1002/ijc.30797 · Cited by 13
Murali, M. R., Kratz, A., & Finberg, K. E. (2006) · New England Journal of Medicine · doi:10.1056/nejmcpc069031 · Cited by 13
Roghani, S. A., Lotfi, R., Soleymani, B., Samimi, Z., Feizollahi, P., Asar, S., Abdan, Z., Khorasanizadeh, A., & Taghadosi, M. (2023) · Clinical Rheumatology · doi:10.1007/s10067-023-06521-y · Cited by 13
Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes
Ouni, M., Eichelmann, F., Jähnert, M., Krause, C., Saussenthaler, S., Ott, C., Gottmann, P., Speckmann, T., Huypens, P., Wolter, S., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101774 · Cited by 13
Steinvil, A., Rogowski, O., Banai, S., Leshem‐Rubinow, E., Halkin, A., Keren, G., Finkelstein, A., Mashav, N., Zuzut, M. E., Berliner, S. A., et al. (2013) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0b013e32836380b4 · Cited by 13
A role for hepcidin in the anemia caused by Trypanosoma brucei infection
Neves, J. V., Gomes, A. C., Costa, D. M., Barroso, C., Vaulont, S., Cordeiro‐da‐Silva, A., Tavares, J., & Rodrigues, P. (2020) · Haematologica · doi:10.3324/haematol.2019.227728 · Cited by 13
Martínez, D. P., Oliver, C., Santibáñez, N., Coronado, J. L., Oyarzún, R., Enríquez, R., Vargas‐Chacoff, L., & Romero, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.849752 · Cited by 14
Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation
Min, K.-S., Takano, M., Amako, K., Ueda, H., & Tanaka, K. (2013) · Toxicology Letters · doi:10.1016/j.toxlet.2013.01.010 · Cited by 13
Moncayo, R., & Moncayo, H. (2007) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-8-17 · Cited by 13
Moreno‐Fernández, J., Díaz‐Castro, J., Alférez, M. J. M., Nestares, T., Ochoa, J. J., Sánchez-Alcover, A., & López‐Aliaga, I. (2015) · Food & Function · doi:10.1039/c5fo01299f · Cited by 13
Fukuda, T., Ueda, K., Ishiyama, T., Goto, R., Muramatsu, S., Hashimoto, M., Watanabe, K., & Tanaka, N. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.03.056 · Cited by 13
Bexkens, M. L., van Gestel, R. A., van Breukelen, B., Urbanus, R. T., Brouwers, J. F. H. M., Nieuwland, R., Tielens, A. G. M., & van Hellemond, J. J. (2020) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2020.111296 · Cited by 13
“for which several causes have been postulated including malnutrition, blood loss and restricted erythropoiesis due to inflammation [49,50].”
BackgroundComparative analysis of Xenopus tropicalis hepcidin I and hepcidin II genes
Hu, X., Ward, C. K., Aono, S., 兰利琼, Dykstra, C. C., Kemppainen, R. J., Morrison, E. E., & Shi, J. N. (2008) · Gene · doi:10.1016/j.gene.2008.08.022 · Cited by 13
El-Maleky, N. F., & Ebrahim, R. H. (2018) · Electromagnetic Biology and Medicine · doi:10.1080/15368378.2018.1531423 · Cited by 13
“IL6 is a proinflammatory cytokine which is a potent stimulus of hepcidin production (Nemeth et al., 2004).”
BackgroundIron and the Reticuloendothelial System
Weiß, G. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_11 · Cited by 13
Puyvelde, K. V., Cytryn, E., Mets, T. F., & Beyer, I. (2009) · Acta Clinica Belgica · doi:10.1179/acb.2009.047 · Cited by 13
“An impaired induction of EPO by low hemoglobin levels has been described due to infl ammation (29, 31).”
BackgroundIron Metabolism following Twice a Day Endurance Exercise in Female Long-Distance Runners
Ishibashi, A., Maeda, N., Kojima, C., & Goto, K. (2022) · Nutrients · doi:10.3390/nu14091907 · Cited by 13
A compartmental model of iron regulation in the mouse
Lao, B. J., & Kamei, D. T. (2006) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2006.06.033 · Cited by 13
Bıçakçı, Z., Tavil, B., Tezer, H., & Olcay, L. (2013) · The Turkish Journal of Pediatrics · doi:10.24953/turkjpediatr.2013.1511 · Cited by 13
Prolonged Chronic Stress and Persistent Iron Dysregulation Prevent Anemia Recovery Following Trauma
Apple, C. G., Miller, E., Kannan, K. B., Thompson, C. W., Darden, D. B., Efron, P. A., & Mohr, A. M. (2021) · Journal of Surgical Research · doi:10.1016/j.jss.2021.05.034 · Cited by 13
Fisher, A. L., Wang, C., Xu, Y., Phillips, S., Paulo, J. A., Małachowska, B., Xiao, X., Fendler, W. M., Mancias, J. D., & Babitt, J. L. (2023) · iScience · doi:10.1016/j.isci.2023.108555 · Cited by 13
Iron homeostasis governs erythroid phenotype in Polycythemia Vera
Bennett, C., Jackson, V. E., Pettikiriarachchi, A., Hayman, T., Schaeper, U., Moir-Meyer, G., Fielding, K., Ataíde, R., Clucas, D. B., Baldi, A., et al. (2023) · Blood · doi:10.1182/blood.2022016779 · Cited by 13
“Hepcidin is also upregulated by inflammation 16 (via IL6-driven JAK-STAT signaling 17 ).”
Iron Deficiency and Iron Deficiency Anemia in Chronic Disease—Common, Important, and Treatable
Moum, B. A., & Lindgren, S. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134519 · Cited by 13
COVID-19 compromises iron homeostasis: Transferrin as a target of investigation
Gaiatto, A. C. M., Bibo, T. A., Costa, N. D. G. M. E., Raimundo, J. R. S., Alves, B. D. C. A., Gascón, T. M., de Carvalho, S. S., Pereira, E. C., Fonseca, F. L. A., & da Veiga, G. L. (2022) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2022.127109 · Cited by 15
Azcárate, I. G., Sánchez-Jaut, S., Marín-García, P., Linares, M., Pérez-Benavente, S., García-Sánchez, M., Uceda, J., Kamali, A. N., Morán-Jiménez, M.-J., Puyet, A., et al. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.09.027 · Cited by 12
“For instance, the peptide hepcidin, a key mammalian inhibitor of the iron entry into serum, is induced by interleukins during infection and inflammation [4, 6, 7].”
BackgroundDietary and Sentinel Factors Leading to Hemochromatosis
Oh, C.-K., & Moon, Y. (2019) · Nutrients · doi:10.3390/nu11051047 · Cited by 12
“In contrast, dietary iron deficiency decreases hepcidin production, leading to intestinal iron absorption and iron release from macrophages so that more iron is available for the body’s needs [10,71,72].”
BackgroundIL-18 Binding Protein–Producing Cells Attenuate Anemia in Murine Macrophage Activation Syndrome
Harel, M., Fauteux‐Daniel, S., Rodriguez, E., Palmer, G., & Gabay, C. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2300065 · Cited by 12
Disruption of the potassium channel regulatory subunit KCNE2 causes iron-deficient anemia
Salsbury, G., Cambridge, E. L., McIntyre, Z., Arends, M. J., Karp, N. A., Isherwood, C. M., Shannon, C., Hooks, Y. E., Ramírez‐Solis, R., Adams, D. J., et al. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.07.269 · Cited by 13
Belot, A., Gourbeyre, O., Palin, A., Rubio, A., Largounez, A., Besson‐Fournier, C., Latour, C., Lorgouilloux, M., Gallitz, I., Montagner, A., et al. (2020) · Haematologica · doi:10.3324/haematol.2019.237321 · Cited by 14
“Hepcidin production by the hepatocytes is induced by a number of stimuli, most notably iron, through the BMP-SMAD signaling pathway,(3) and inflammatory signals, through the IL-6/ STAT3 signaling axis.(4) In addition, hepcidin has also been reported to respond to intracellular stress, namely endoplasmic reticulum (ER)…”
BackgroundOchola, L., Ayieko, C., Kisia, L. E., Magak, N. G., Shabani, E., Ouma, C., & John, C. C. (2014) · Infection and Immunity · doi:10.1128/iai.01924-14 · Cited by 12
Laudisio, D., de Alteriis, G., Vetrani, C., Aprano, S., Pugliese, G., Zumbolo, F., Colao, A., & Savastano, S. (2023) · Nutrients · doi:10.3390/nu15214702 · Cited by 12
“In addition, interleukin (IL)-6 also modulates the concentration and biological activity of hepcidin, a peptide hormone mainly produced by the liver that reduces iron efflux from hepatocytes and duodenal iron absorption by reducing the stability of the ferroportin transporter [17–19].”
BackgroundSasaki, Y., Noguchi‐Sasaki, M., Matsuo-Tezuka, Y., Matsumoto-Omori, Y., Kurasawa, M., Yorozu, K., & Shimonaka, Y. (2014) · International Journal of Hematology · doi:10.1007/s12185-014-1554-6 · Cited by 12
“Hepcidin is involved in various disorders such as the anemia of chronic disease, in which inflammatory cytokines such as interleukin (IL)-6 and IL-1b up-regulate hepcidin expression and thus cause functional iron-deficiency anemia [20, 21].”
BackgroundRibeiro, S., Garrido, P., Fernandes, J. C., Vala, H., Rocha‐Pereira, P., Costa, E. M., Belo, L., Reis, F., & Santos‐Silva, A. (2016) · Biochimie · doi:10.1016/j.biochi.2016.03.012 · Cited by 12
“increased levels of hepcidin [18]; this liver pepti de regulates iron metabolism by degrading ferroportin (an iron exporter), present i the membrane surface of enterocytes, hepatocytes and macrophages; thus, hep cidin controls iron absorption and mobilization from iron stores [19,20].”
BackgroundTo induce or not to induce: the fight over hepcidin regulation
Sangkhae, V., & Nemeth, E. (2019) · Haematologica · doi:10.3324/haematol.2019.216960 · Cited by 12
“regulation by infection and inflammation is mediated in large part by IL-6.(14) IL-6 binding to its receptor, IL-6Rα, and co-receptor, gp130, results in phosphorylation of JAK1/2 in hepatocytes, which then phosphorylates”
BackgroundSelf-citationQuantitative assay of urinary hepcidin using MALDI-TOF mass spectrometry
Gay, M. C. L., Mullaney, I., Trinder, D., Olynyk, J. K., & Trengove, R. D. (2009) · Analytical Methods · doi:10.1039/b9ay00130a · Cited by 12
Anemia in monkey collagen-induced arthritis is correlated with serum IL-6, but not TNFα
Uchiyama, Y., Koike, N., & Mihara, M. (2008) · Rheumatology International · doi:10.1007/s00296-008-0547-2 · Cited by 12
“As IL-6 induces hepcidin production from liver cells [ 23 ], we are now examining the involvement of hepcidin in monkey CIA.”
BackgroundIncreased hepcidin expression in multibacillary leprosy
de Souza, V. N. B., Malaspina, T. S. D. S., Campanelli, A. P., Ghidella, C. C., Ura, S., Dalpino, D., do Nascimento, D. C., & Latini, A. C. P. (2012) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762012000900026 · Cited by 12
“The levels of urinary hepcidin were measured as described previously (Nemeth et al. 2004) at University of California (Los Angeles, CA, USA) by Dr Seth Rivera.”
BackgroundMethodIL-6 Blockers in Systemic Onset Juvenile Idiopathic Arthritis
Barone, P., Pignataro, R., Garozzo, M. T., & Leonardi, S. (2015) · Immunotherapy · doi:10.2217/imt.15.104 · Cited by 12
Zhang, J., Gong, F., Li, L., Zhao, M., Wu, Z., & Song, J. (2015) · PubMed · Cited by 12
Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?
Patel, M. S., McKie, E., Steiner, M., Pascoe, S., & Polkey, M. (2019) · BMJ Open Respiratory Research · doi:10.1136/bmjresp-2019-000454 · Cited by 12
“46 47 These different underlying causes of anaemia conferred by chronic systemic inflammation are seen in a variety of conditions, thus impairing normal corrective mechanisms and they are also relevant in chronic lung disease (figure 4).”
Hosoki, T., Ikuta, K., Shimonaka, Y., Sasaki, Y., Yasuno, H., Sato, K., Ohtake, T., Sasaki, K., Torimoto, Y., Saito, K., et al. (2009) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200900112 · Cited by 12
“BMP2 and holo-transferrin (holo-Tf) were purchased from R & D Systems; IL-6 was obtained from Wako Pure Chemical Industries, Osaka, Japan.”
BackgroundInfluentialCarence martiale fonctionnelle, inflammation et fatigue après radiothérapie
Grellier, N., Deray, G., Yousfi, A., Khodari, W., Bouaita, R., & Belkacémi, Y. (2015) · Bulletin du Cancer · doi:10.1016/j.bulcan.2015.06.001 · Cited by 12
Sebastiani, G., & Pantopoulos, K. (2010) · CRC Press eBooks · doi:10.1201/9781420059984-c13 · Cited by 12
The Anemia of Inflammation and Chronic Disease
Roy, C. N. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_15 · Cited by 12
Bonnah, R. A., Hoelter, J., Steeghs, L., Enns, C. A., So, M., & Muckenthaler, M. U. (2005) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00519.x · Cited by 12
“Examples include anti-apoptotic protein A20 (Mataki et al., 2000), VEGF (Ko et al., 1999), apoptosisassociated speck-like protein (ASC) (Stehlik et al., 2002), PLOD-2 (Ah-Kim et al., 2000), Prolyl-4-hydroxylase (Kawaguchi et al., 1992); and haem oxygenase-1 (HOX-1) (Oguro et al., 2002).”
L'hepcidine et le métabolisme du fer
Delaby, C., Deybach, J., & Beaumont, C. (2007) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2007.03.009 · Cited by 12
Zheng, H., Yang, F., Deng, K., Wei, J., Liu, Z., Zheng, Y., & Xu, H. (2023) · Medicine · doi:10.1097/md.0000000000033225 · Cited by 12
“Elizabeta[19] proved that IL-6 is necessary to induce hepcidin during inflammation, and the cytokine itself can rapidly induce iron deficiency anemia.”
BackgroundExercise and Heat Stress: Inflammation and the Iron Regulatory Response
McKay, A. K. A., McCormick, R., Tee, N., & Peeling, P. (2021) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2021-0080 · Cited by 12
The link between ferroptosis and airway inflammatory diseases: A novel target for treatment
Lin, Z., Yang, X., Guan, L., Qin, L., Ding, J., & Zhou, L. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.985571 · Cited by 13
“, 1994); on the other hand, IL-6 can induce the synthesis of ferroregulin (Nemeth et al., 2004), an inhibitor of iron transport proteins, which leads to cellular iron accumulation.”
BackgroundStealthy microbes: How Neisseria gonorrhoeae hijacks bulwarked iron during infection
Stoudenmire, J. L., Greenawalt, A. N., & Cornelissen, C. N. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.1017348 · Cited by 12
Serum Prohepcidin Levels Are Lower in Patients with Atrophic Gastritis
Kim, H.-K., Jang, E.-C., Yeom, J., Kim, S., Cho, H., Kim, S. S., Chae, H., & Cho, Y. (2013) · Gastroenterology Research and Practice · doi:10.1155/2013/201810 · Cited by 12
López‐Aliaga, I., García-Pedro, J. D., Moreno‐Fernández, J., Alférez, M. J. M., López‐Frías, M., & Díaz‐Castro, J. (2018) · Food & Function · doi:10.1039/c8fo00552d · Cited by 12
Moldal, E. R., Kjelgaard-Hansen, M. J., Peeters, M. E., Nødtvedt, A., & Kirpensteijn, J. (2018) · Acta veterinaria Scandinavica · doi:10.1186/s13028-018-0384-6 · Cited by 12
“indicates that hypoferremia is mediated by interleukin 6 (IL-6) because it induces synthesis of the iron regulatory hormone hepcidin, an acute phase protein in humans [46, 47].”
BackgroundAdrenergic Modulation of Erythropoiesis After Trauma
Munley, J. A., Kelly, L. S., & Mohr, A. M. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.859103 · Cited by 12
“Proinflammatory signaling factors promote myeloid lineage expansion at the expense of erythroid progenitors (IL-1α, IL-1β), induce production of ironsequestering peptide hepcidin (IL-6) that leads to inappropriate hypoferremia in the setting of acute blood loss anemia, and directly inhibit erythroid progenitor growth…”
BackgroundInfluentialShort-Term Effects of Blood Transfusions on Hepcidin in Preterm Infants
Springer, L., Müller, K., Poets, C. F., Peter, A., Olbina, G., Westerman, M. E., & Franz, A. R. (2015) · Neonatology · doi:10.1159/000437132 · Cited by 12
von Roedern, M., Buriko, Y., Prittie, J. E., & Lamb, K. E. (2017) · Journal of Small Animal Practice · doi:10.1111/jsap.12658 · Cited by 12
“This is caused by sequestration of iron into tissues, which is mediated by inflammatory cytokines, primarily IL-6 ( Nemeth et al. 2004 ) .”
BackgroundDisentangling Anemia in Frailty: Exploring the Role of Inflammation
Herpich, C., Göger, L., Faust, L., Kalymon, M., Ott, C., Walter, S., Lehmkuhl, E., Grune, T., Moskiou, V., Müller‐Werdan, U., et al. (2024) · The Journals of Gerontology Series A · doi:10.1093/gerona/glae243 · Cited by 12
Murusuri, A. B., & Tang, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1742656 · Cited by 12
Dual role of hepcidin in response to pathogens
Navidifar, T., Meftah, E., Baghsheikhi, H., Kazemzadeh, K., Karimi, H., & Rezaei, N. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.107496 · Cited by 13
Mohamed, D. A., Hanfy, E., & Fouda, K. A. (2018) · Journal of Biological Sciences · doi:10.3923/jbs.2018.317.328 · Cited by 12
Ferritin in ferroptosis: implications for neurodegenerative diseases (Review)
Chen, W., Tian, H., Wei, R., Chen, X., & Jia, Y. (2026) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2026.5790 · Cited by 12
Unraveling Hepcidin Plasma Protein Binding: Evidence from Peritoneal Equilibration Testing
Diepeveen, L. E., Laarakkers, C. M., Peters, H. P. E., van Herwaarden, A. E., Groenewoud, H., IntHout, J., Wetzels, J. F., van Swelm, R. P. L., & Swinkels, D. W. (2019) · Pharmaceuticals · doi:10.3390/ph12030123 · Cited by 11
“Theoretically, this potential of a fast production [33,35,37] and quick turnover of hepcidin would preclude the need for protein binding [30].”
BackgroundWei, J., Xiang, J., Hao, Y., Si, J., Wang, W., Li, F., & Song, Z. (2022) · BMC Pulmonary Medicine · doi:10.1186/s12890-022-02158-w · Cited by 11
“Previous studies have shown that CRA may be related to the activation of cytokines such as interferon-γ, interleukin-1, and tumor necrosis factor, which may inhibit the production of endogenous erythropoietin, impair iron use, and reduce the proliferation of erythrocyte precursors [12, 13].”
BackgroundMarrow failure and aging: The role of “Inflammaging”
Zhao, J., Ghimire, A., & Liesveld, J. L. (2021) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2021.101283 · Cited by 12
Belay, E., Endrias, A., Alem, B., & Endris, K. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204791 · Cited by 11
Molecular basis of hereditary iron homeostasis defects
Horváthová, M., Ponka, P., & Divoký, V. (2010) · Hematology · doi:10.1179/102453310x12583347009810 · Cited by 12
Interleukin-6 and Lipopolysaccharide Modulate Hepcidin mRNA Expression by Hepg2 Cells
Villarroel, P., Blanc, S. L., & Arredondo, M. (2012) · Biological Trace Element Research · doi:10.1007/s12011-012-9522-6 · Cited by 11
Differential effects of basolateral and apical iron supply on iron transport in Caco-2 cells
Eady, J. J., Wormstone, Y. M., Heaton, S. J., Hilhorst, B., & Elliott, R. M. (2015) · Genes & Nutrition · doi:10.1007/s12263-015-0463-5 · Cited by 11
“Expression and secretion of hepcidin from the liver is regulated by iron status and inflammation (Mazur et al. 2003; Nemeth et al. 2004a; Nicolas et al. 2002).”
BackgroundAnemia Recovery after Trauma: A Longitudinal Study
Kelly, L. S., Munley, J. A., Kannan, K. B., Pons, E. E., Coldwell, P. S., Bible, L. E., Parvataneni, H. K., Hagen, J. E., Efron, P. A., & Mohr, A. M. (2022) · Surgical Infections · doi:10.1089/sur.2022.299 · Cited by 11
“20,30,31 36 Those subjects with prolonged or no anemia recovery were recognized to have had greater infectious complications, and received more packed red blood cell transfusions, and spent more time in the ICU than those who recovered quickly.”
Apple, C. G., Miller, E., Loftus, T. J., Kannan, K. B., Thompson, C. W., López, M. C., Baker, H. V., Moldawer, L. L., Efron, P. A., & Mohr, A. M. (2019) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2019.09.011 · Cited by 11
“(16–19) IL-6 upregulates hepcidin production, leading to the sequestration of iron in macrophages, and also activates secretion of CRP.(20, 21) Norepinephrine, a key modulator of hematopoietic progenitor mobilization and an inhibitor of bone marrow erythroid cell growth at high levels, also directly stimulates IL-6 re…”
BackgroundDowsett, J., Didriksen, M., Larsen, M. H., Burgdorf, K. S., Thørner, L. W., Sørensen, E., Erikstrup, C., Pedersen, O. B., Ostrowski, S. R., & Ullum, H. (2021) · Sleep Medicine · doi:10.1016/j.sleep.2021.10.008 · Cited by 11
Systemic Iron Deficiency in a Nonhuman Primate Model of Endometriosis
Atkins, H., Appt, S. E., Taylor, R. N., Torres-Mendoza, Y., Lenk, E. E., Rosenthal, N. S., & Caudell, D. L. (2018) · Comparative Medicine · doi:10.30802/aalas-cm-17-000082 · Cited by 11
Mieszkowski, J., Kochanowicz, M., Żychowska, M., Kochanowicz, A., Grzybkowska, A., Anczykowska, K., Sawicki, P., Borkowska, A., Niespodziński, B., & Antosiewicz, J. (2019) · BioMed Research International · doi:10.1155/2019/9576876 · Cited by 11
“The inflammation process is strictly connected with iron metabolism [9].”
BackgroundPhan-Aram, P., Mahasri, G., Kayansamruaj, P., Amparyup, P., & Srisapoome, P. (2020) · Biomolecules · doi:10.3390/biom10081132 · Cited by 11
Banaszkiewicz, M., Małyszko, J., Batko, K., Koc‐Żórawska, E., Żórawski, M., Dumnicka, P., Jurczyszyn, A. J., Woziwodzka, K., Tisończyk, J., Krzanowski, M., et al. (2020) · Mediators of Inflammation · doi:10.1155/2020/5657864 · Cited by 11
“BM stromal cells have been reported as a major source of interleukin 6, which is a key player of inflammatory pathways in myeloma [28, 29] and inducer of hepcidin [30], which further emphasizes the importance of the abnormal ME.”
BackgroundPratummo, K., Jetsrisuparb, A., Fucharoen, S., & Tripatara, A. (2013) · Hematology · doi:10.1179/1607845413y.0000000110 · Cited by 11
Chlamydophila pneumoniae changes iron homeostasis in infected tissues
Edvinsson, M., Frisk, P., Boman, K., Tallkvist, J., & Ilbäck, N. (2008) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2008.01.014 · Cited by 11
“…to infection and inflammation and exert a negative effect on Fe efflux ARTICLE IN PRESS M. Edvinsson et al. / International Journal of Medical Microbiology 298 (2008) 635–644642 from macrophages, hepatocytes, and enterocytes by binding to the Fe transporter Ferroportin 1 (Nemeth et al., 2004).”
BackgroundHuang, X., Fung, E. T., Yip, C., & Zeleniuch‐Jacquotte, A. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2008.06.009 · Cited by 11
In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation
Viatte, L., Gröne, H.-J., Hentze, M. W., & Galy, B. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0494-8 · Cited by 11
“Our results show that both IRP1- and IRP2-deficient mice can mount an appropriate response to aseptic local inflammation with the recruitment of leukocytes to the site of inflammation, an increase in serum IL6, a decrease in serum iron levels, and an increase in the hepatic expression of mRNAs encoding acute phase pro…”
BackgroundInfluentialIntravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation
Lofruthe, N., Gallitz, I., Traeger, L., Bäumer, N., Schulze, I., Kuhlmann, T., Müller‐Tidow, C., & Steinbicker, A. U. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158599 · Cited by 11
“The inflammatory cytokine interleukin-6 (IL-6) increases expression of the iron regulatory hormone hepcidin [3, 4, 5, 6].”
BackgroundIron deficiency anemia, anemia of chronic disorders and iron overload
Pippard, M. J. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7020-3147-2.00011-0 · Cited by 13
Ramasamy, J., Jagadish, C., Sukumaran, A., Varghese, J., Mani, T., Joseph, A. J., Simon, E. G., & Jacob, M. (2023) · Inflammation · doi:10.1007/s10753-023-01872-9 · Cited by 11
“It would have been advantageous to have had serum IL-6 concentrations as well, as a marker of inflammation in this context, as it is known to directly regulate hepcidin transcription [25].”
BackgroundWu, X., Cap, A. P., Bynum, J. A., Chance, T. C., Darlington, D. N., & Meledeo, M. A. (2024) · Scientific Reports · doi:10.1038/s41598-024-53945-w · Cited by 11
“Since the expression of EPO and hepcidin could be upregulated by multiple factors (such as proinflammatory cytokines) after trauma and hemorrhage 35,36 , the tendency toward higher expression of EPO and hepcidin in MK-treated rats may not be solely the result of HIF-1α by MK treatment.”
Patel, H., Minkah, N. K., Kumar, S., Zanghì, G., Schepis, A., Goswami, D., Armstrong, J., Abatiyow, B. A., Betz, W., Reynolds, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46270-3 · Cited by 11
“The major pathways that drive hepcidin expression are interleukin-6 (IL-6) and bone morphogenetic protein (BMP) receptor-mediated signaling during in fl ammation 13,14 .”
BackgroundEarly life stress and iron metabolism in developmental psychoneuroimmunology
Reid, B. M. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100824 · Cited by 13
“IL-6, crucial for hepcidin synthesis, increases with acute and chronic stress (Bower and Kuhlman, 2023; Marsland et al., 2017; Nemeth et al., 2004).”
Coimbra, S., Ferreira, C., Belo, L., Rocha‐Pereira, P., Catarino, A., Monteiro, L., Catarino, C., & Santos‐Silva, A. (2017) · Journal of Investigative Medicine · doi:10.1136/jim-2017-000528 · Cited by 11
Iron homeostasis is dysregulated, but the iron-hepcidin axis is functional, in chronic liver disease
Varghese, J., Varghese, J., Karthikeyan, M., Rasalkar, K., Raghavan, R., Sukumaran, A., Premkumar, P. S., Eapen, C., & Jacob, M. (2019) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2019.126442 · Cited by 12
Fehsel, K. (2024) · Biomedicines · doi:10.3390/biomedicines12102294 · Cited by 11
“IL6 and Cyp1B1 increase the hepatic production of hepcidin [154], which downregulates the iron uptake in the duodenum.”
BackgroundDiepeveen, L. E., Stegemann, G., Wiegerinck, E. T. G., Roelofs, R., Naber, M. R., Loréal, O., Smeets, B., Thévenod, F., Swinkels, D. W., & van Swelm, R. P. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031352 · Cited by 11
“Interestingly, although inflammation is a known potent inducer of hepcidin in hepatocytes via IL-6 signaling [36], Hamp1 expression was not affected by IL-6 or LPS in distal tubular epithelial cells during 4-h incubations.”
BackgroundHepcidin and Iron Deficiency in Women One Year after Sleeve Gastrectomy: A Prospective Cohort Study
Lefèbvre, T., Coupaye, M., Esposito‐Farèse, M., Gault, N., Talbi, N., Quintin, C., Schmitt, C., Bekri, S., Bado, A., Puy, H., et al. (2021) · Nutrients · doi:10.3390/nu13082516 · Cited by 11
“Indeed, hepcidin is an acute phase protein and its production can be induced by multiple stimuli especially IL-6, which is higher in our patients before surgery [37].”
BackgroundInfluentialExercise-modulated IL-6 in cancer cachexia: molecular mechanisms and therapeutic potential
Wei, S., Lv, X., Xu, Y., & Ding, S. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07690-5 · Cited by 12
RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease
Fujii, T., Kobayashi, K., Kaneko, M., Osana, S., Tsai, C.-T., Ito, S., & Hata, K. (2024) · Immuno · doi:10.3390/immuno4030017 · Cited by 11
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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