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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Correlation Between Serum Ferritin and Viral Hepatitis in Thalassemia Patients
Rujeerapaiboon, N., Tantiworawit, A., Piriyakhuntorn, P., Rattanathammethee, T., Hantrakool, S., Chai‐Adisaksopha, C., Rattarittamrong, E., Norasetthada, L., Fanhchaksai, K., & Charoenkwan, P. (2021) · Hemoglobin · doi:10.1080/03630269.2021.1926277 · Cited by 11
Iron metabolism and maternal-fetal iron circulation
Słomka, A., Żekanowska, E., Piotrowska, K., & Kwapisz, J. (2012) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.5604/17322693.1019651 · Cited by 11
A Comprehensive Index for Predicting Risk of Anemia from Patients' Diagnoses
Tuck, M., Alemi, F., Shortle, J., Avramovic, S., & Hesdorffer, C. (2017) · Big Data · doi:10.1089/big.2016.0073 · Cited by 11
Goto, K., Kasai, N., Kojima, C., & Ishibashi, A. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2017-0418 · Cited by 11
Kaushik, S. R., Sahu, S., Guha, H., Saha, S. T., Das, R., Kupa, R.-U., Kapfo, W., Deka, T., Basumatary, R., Thong, A., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.985538 · Cited by 10
Tallec-Estève, N. L., Rousseau, C., Desrues, B., Loréal, O., & Thibault, R. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.06.007 · Cited by 10
Cui, F., Guo, J., Hu, H., Zhang, Y., & Shi, M. Y. (2020) · Journal of Inflammation · doi:10.1186/s12950-020-00265-1 · Cited by 10
“Hepcidin regulate the release of cellular iron and body iron homeostasis [5, 6], which is regulated by iron level, inflammation, erythropoietin (Epo) and hypoxia [7, 8] .”
BackgroundIron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions
Ryan, E. K., Clutter, C., Barra, C. D., Jenkins, B., O’Shaughnessy, S., Ryan, O. K., McKenna, C., Heneghan, H., Walsh, F., Finlay, D. K., et al. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2300649 · Cited by 10
Kim, B., Park, S. J., Hong, S. P., Cheon, J. H., Kim, T. I., & Kim, W. H. (2015) · Gut and Liver · doi:10.5009/gnl14193 · Cited by 10
Goyal, H., Mohanty, S., Sharma, M., & Rani, A. A. (2017) · Indian Journal of Nephrology · doi:10.4103/0971-4065.179301 · Cited by 10
“[10] Hepcidin expression is upregulated by inflammation[11] and iron loading[12] and downregulated by erythropoietic activity.”
BackgroundIfeanyi, O. E., Felix, C. E., Ochiabuto, M. T. B., Ugwuja, M. C., Nchekwubedi, C. S., & Chinedum, O. K. (2021) · African Journal of Biological Sciences · doi:10.33472/afjbs.3.1.2021.146-156 · Cited by 10
“Hepcidin breaks the major cellular iron exporter ferroportin resulting to decreased iron absorption in the intestine and iron retention in monocytes and macrophages and the spleen (Nemeth et al., 2004).”
BackgroundMethodFree Radical and Viral Infection: A Review from the Perspective of Ferroptosis
Jun, C., Fu, J., Zhao, S., Zhang, X., Chao, Y., Pan, Q., Sun, H., Zhang, J., Li, B., Xue, T., et al. (2023) · Veterinary Sciences · doi:10.3390/vetsci10070456 · Cited by 10
Rivara, M. B., Ikizler, T. A., Ellis, C. D., Mehrotra, R., & Himmelfarb, J. (2015) · BMC Nephrology · doi:10.1186/s12882-015-0074-9 · Cited by 10
“Inflammation has in turn been shown to lead to activation of macrophages with removal of circulating erythrocytes, down-regulation of erythropoietin receptors, and dysregulated cell signaling following activation of the erythropoietin receptor [26, 27].”
BackgroundPunduk, Z., Oral, O., Ozkayin, N., Rahman, K., & Varol, R. (2015) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2014.11.005 · Cited by 10
“Hepcidin is a liver-produced peptide hormone, up-regulated in response to elevated iron levels and the inflammatory cytokine interleukin-6 (IL-6),(13,14) and an increase in hepcidin levels usually occurs as a homeostatic response to inflammatory stimuli namely the IL-6 or elevated iron levels.(13) Peeling et al.”
BackgroundVallet, N. (2017) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2017.05.008 · Cited by 10
“…Érythropoïèse Tanno et al. (2012) [22] Foie Hepcidine Dégradation de la ferroportine (séquestration et diminution des apports de fer) Inflammation Nemeth et al. (2004) [14] Fer lié à la transferrine Fer intracellulaire Rein EPO Stimulation de l’érythropoïèse Hypoxie (HIF) Semenza et al.…”
Yu, C., Cao, J., Wang, L., Yang, Y., Ni, Y., & Wang, J. (2018) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-018-1307-0 · Cited by 10
Identification of The Canidae Iron Regulatory Hormone Hepcidin
Mead, M. K., Claus, M. A., Litton, E., Smart, L., Raisis, A. L., Rossi, G., Trengove, R. D., & Gummer, J. P. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-55009-w · Cited by 10
LPS Modulates the Expression of Iron-Related Immune Genes in Two Antarctic Notothenoids
Martínez, D. P., Sousa, C., Oyarzún, R., Pontigo, J. P., Canário, A. V. M., Power, D. M., Vargas‐Chacoff, L., & Guerreiro, P. M. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00102 · Cited by 10
Alghamdi, T. H., & Atta, I. S. (2020) · PubMed Central · Cited by 10
Serum Iron and Ferritin Levels Are Correlated with Complement C3
Wen, S., Sha, Y., Li, Y., Rui, Z., Si, C., Zhou, Y., Yan, F., Wang, B., Hu, J., Han, X., et al. (2020) · Biological Trace Element Research · doi:10.1007/s12011-020-02379-2 · Cited by 11
Huang, H., Zuzarte‐Luís, V., Fragoso, G., Calvé, A., Hoang, T. A., Oliero, M., Chabot‐Roy, G., Mullins‐Dansereau, V., Lesage, S., & Santos, M. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-78037-3 · Cited by 10
Association of vitamin A with anemia and serum hepcidin levels in children aged 6 to 59 mo
Silva, A. D. P., Pereira, A. D. S., Simões, B. F. T., Omena, J., Rodrigues, C. D. S. C., de Castro, I. R. R., & Citelli, M. (2021) · Nutrition · doi:10.1016/j.nut.2021.111463 · Cited by 10
Srai, S. K., & Sharp, P. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_1 · Cited by 11
p,p′-DDT induces microcytic anemia in rats
Tomita, M., Yoshida, T., Fukumori, J., Yamaguchi, S., Kojima, S., Fukuyama, T., Ohnuma-Koyama, A., Takahashi, N., Kashimoto, Y., Kuwahara, M., et al. (2013) · The Journal of Toxicological Sciences · doi:10.2131/jts.38.775 · Cited by 10
Malhotra, R., Kapoor, A., Grover, V., Grover, D., & Kaur, A. (2012) · PubMed · Cited by 10
Postl, A., Zifko, C., Hartl, R. T., Ebel, T., Miller, I., Moldzio, R., Redl, H. R., Kozlov, A. V., Bahrami, S., & Duvigneau, J. C. (2011) · Shock · doi:10.1097/shk.0b013e318231822d · Cited by 10
“(26), our findings of decreased TFBI levels could be explained by increased levels of proinflammatory mediators, a characteristic of HTS, including our model (21).”
BackgroundLi, S., Nakayama, T., Akinc, A., Wu, S., & Karger, B. L. (2014) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2014.09.008 · Cited by 10
“Abnormal high levels of hepcidin can significantly cause reduction in the plasma iron concentration, leading to iron deficiency and thus anemia (Ganz & Nemeth, 2011; Nemeth & Rivera, 2004).”
BackgroundSerum prohepcidin concentrations at birth and 1 month after birth in premature infants
Kitajima, J., Ohga, S., Kinjo, T., Ochiai, M., Takahata, Y., Honjo, S., & Hara, T. (2010) · Pediatric Blood & Cancer · doi:10.1002/pbc.22773 · Cited by 10
“levels, and interleukin-6 according to the iron need [10].”
BackgroundInflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice
Sukumaran, A., Venkatraman, A., & Jacob, M. (2012) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2012.03.002 · Cited by 10
Banerjee, R., Kanak, K., Patel, B., Samanta, M., & Das, S. (2019) · 3 Biotech · doi:10.1007/s13205-019-1874-6 · Cited by 10
Merchant, M. L., Gawęda, A. E., Dailey, A. J., Wilkey, D. W., Zhang, X., Rovin, B. H., Klein, J. B., & Brier, M. E. (2010) · Kidney International · doi:10.1038/ki.2010.468 · Cited by 10
Goto, K., Sumi, D., Kojima, C., & Ishibashi, A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183629 · Cited by 10
Identification, sequencing, and cellular localization of hepcidin in guinea pig (Cavia porcellus)
Schwarz, P., Strnad, P., Singer, N., Oswald, F., Ehehalt, R., Adler, G., & Kulaksiz, H. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0191 · Cited by 11
Ganz, T. (2010) · Wiley eBooks · doi:10.1002/9781444318531.ch13 · Cited by 10
Self-citationWill Targeting Interleukin-6 in the Anemia of CKD Change Our Treatment Paradigm?
Coyne, D. W., & Fleming, R. E. (2020) · Journal of the American Society of Nephrology · doi:10.1681/asn.2020101476 · Cited by 10
Rai, S., & Kar, A. C. (2016) · AYU (An International Quarterly Journal of Research in Ayurveda) · doi:10.4103/ayu.ayu_186_13 · Cited by 10
“AYU ¦ Volume 37 ¦ Issue 1 ¦ January‐March 2016 20 and adrenal glands.[24,25] IL6 has been shown to stimulate the hepcidin expression in vitro and in vivo:[26] which may be the mechanism responsible here also for the up regulation of hepcidin, collectively leading to the hypoferremia and hepatic iron storage.”
BackgroundEnvIRONmental Aspects in Myelodysplastic Syndrome
Petzer, V., Theurl, I., Weiß, G., & Wolf, D. G. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105202 · Cited by 10
Tocilizumab in the treatment of systemic juvenile idiopathic arthritis
Murakami, M., Tomiita, M., & Nishimoto, N. (2012) · Open Access Rheumatology : Research and Reviews · doi:10.2147/oarrr.s21969 · Cited by 17
“35 In addition, IL-6 can induce vascular endothelial growth factor, which plays a crucial role in the angiogenesis necessary for synovial pannus formation and causes joint destruction.”
Dietary Iron and the Elite Dancer
Attwell, C., Dugan, C., McKay, A. K. A., Nicholas, J., Hopper, L., & Peeling, P. (2022) · Nutrients · doi:10.3390/nu14091936 · Cited by 11
“Interestingly, the inflammatory cytokine interleukin-6 (IL-6) released in response to inflammation or infection causes the upregulation of hepcidin [83], and the inflammatory nature of exercise has been shown to elicit a similar response.”
BackgroundIroning out exercise on immuno-oncological outcomes
Soh, J., Lim, Z. X., Lim, E. H., Kennedy, B. K., & Goh, J. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002976 · Cited by 10
Association Between Cytomegalovirus Infection and Bad Obstetric Outcomes in Women from Kirkuk
Hassan, H. M. M., Alsamarai, A. M., Aljumaili, Z. K. M., Alobaidi, A. H., & Al-Salihi, F. G. (2014) · International Journal of Public Health Science (IJPHS) · doi:10.11591/ijphs.v3i1.4672 · Cited by 10
Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism
Horváth, A., Tamási, K., Pap, R., Jánosa, G., & Pandur, E. (2025) · Nutrients · doi:10.3390/nu18010109 · Cited by 12
Intestinal microbiota, immune system and obesity
Álvarez, V. R., Peña, Y. P., & Acosta, M. R. (2010) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 10
Nakamura, M., Imamura, T., Sobajima, M., & Kinugawa, K. (2022) · Heart and Vessels · doi:10.1007/s00380-022-02181-1 · Cited by 10
Nutritional Countermeasures for Spaceflight-Related Stress
Heer, M. A., Baecker, N., Smith, S. M., & Swart, S. R. (2011) · Springer eBooks · doi:10.1007/978-3-642-22272-6_29 · Cited by 10
Macrophages and Iron Metabolism
Ganz, T. (2017) · ASM Press eBooks · doi:10.1128/9781555819194.ch46 · Cited by 10
Self-citationTherapeutic iron restriction in sepsis
Xia, Y., Farah, N., Maxan, A., Zhou, J., & Lehmann, C. (2016) · Medical Hypotheses · doi:10.1016/j.mehy.2016.01.018 · Cited by 9
“well-known anemia of chronic inflammation, due to IL-6-induced hepcidin up-regulation can also contribute to anemia [4,42].”
BackgroundIron deposition in autopsied liver specimens from older patients receiving intravenous iron infusion
Akatsu, H., Manabe, T., Kawade, Y., Tanaka, H., Kanematsu, T., Arakawa, K., Masaki, Y., Hishida, C., Kanesaka, T., Ogawa, N., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0237104 · Cited by 9
Nazemian, V., Kalanaky, S., Manaheji, H. S., Hooshmandi, E., Mohammadi, M., Zaringhalam, J., & Mirjafai, S. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.02.003 · Cited by 9
Dynamics of iron metabolism in patients with bloodstream infections: a time-course clinical study
Moro, H., Bamba, Y., Nagano, K., Hakamata, M., Ogata, H., Shibata, S., Cho, H., Aoki, N., Sato, M., Ohshima, Y., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-46383-7 · Cited by 9
“Acute-phase proteins like CRP, ferritin, hepcidin, and LCN2 are induced by IL-6 3,4,15,26 .”
BackgroundXie, L., Guan, X., Zhou, Y., He, Y., Chen, S., Xiao, W., Yang, J., Lu, J., Hong, L., Hu, Q., et al. (2024) · Nutrients · doi:10.3390/nu16193424 · Cited by 9
Endothelial ZIP8 plays a minor role in BMP6 regulation by iron in mice
Fisher, A. L., Phillips, S., Wang, C., Paulo, J. A., Xiao, X., Moschetta, G. A., Sridhar, A., Mancias, J. D., & Babitt, J. L. (2024) · Blood · doi:10.1182/blood.2023023385 · Cited by 9
An Update on Iron Homeostasis: Make New Friends, but Keep the Old
Roy, C. N. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0000000000000190 · Cited by 9
Hamad, M. A., & Awadallah, S. M. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.10.019 · Cited by 9
“Conversely, inflammatory cytokines (IL-1, IL-6, IL-22, TGF-b1, and TLR5) were shown to associate with increased hepcidin synthesis [54,55] in a JAK-STAT3-dependent manner [56].”
BackgroundGhatpande, N., Apte, P. P., Naik, S. S., Joshi, B. N., Gokhale, M. K., & Kulkarni, P. P. (2016) · Metallomics · doi:10.1039/c6mt00129g · Cited by 9
Yuan, L., Xiu, J., Chen, J., Xie, M., Geng, L., & Gao, R. (2016) · CyTA - Journal of Food · doi:10.1080/19476337.2016.1221858 · Cited by 9
“And its metabolism is regulated by hepcidin and iron export protein ferroportin (FPN1) (Nemeth & Ganz, 2009; Nemeth et al., 2004).”
Backgroundda Silva, A. R., Neves, J. C., Mleczko‐Sanecka, K., Tandon, A., Sauer, S. W., Hentze, M. W., & Muckenthaler, M. U. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1551-3 · Cited by 9
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.2017.10.031 · Cited by 9
Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation
Gallitz, I., Lofruthe, N., Traeger, L., Bäumer, N., Hoerr, V., Faber, C., Kuhlmann, T., Müller‐Tidow, C., & Steinbicker, A. U. (2018) · BMC Physiology · doi:10.1186/s12899-018-0037-z · Cited by 9
“During inflammation, cytokines such as the pro-inflammatory cytokine interleukin 6 (IL-6) are induced [6].”
BackgroundLoomis, W. P., Delaney, M. A., Johnson, M., & Cookson, B. T. (2020) · Infection and Immunity · doi:10.1128/iai.00417-20 · Cited by 9
“IL-6 produced at the site of infection induces hepatic expression of hepcidin, which in turn binds ferroportin to decrease intestinal iron absorption and increase iron retention by macrophages (52).”
BackgroundSakhin, V. T., Grigoriev, M. A., Kryukov, E. V., Казаков, С. П., Sotnikov, A. V., Гордиенко, А. В., & Анатольевич, Р. О. (2020) · Oncohematology · doi:10.17650/1818-8346-2020-15-4-82-90 · Cited by 9
“Помимо этого, ранее показано стимулирующее влияние ИЛ6 на синтез гепцидина [10, 23].”
The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment
Banaszkiewicz, M., Małyszko, J., Batko, K., Koc‐Żórawska, E., Żórawski, M., Dumnicka, P., Jurczyszyn, A. J., Woziwodzka, K., Maleszka, A., Krzanowski, M., et al. (2022) · Medicina · doi:10.3390/medicina58030417 · Cited by 9
Hegelund, M. H., Glenthøj, A. B., Ryrsø, C. K., Ritz, C., Dungu, A. M., Sejdic, A., List, K. C. K., Krogh‐Madsen, R., Lindegaard, B., Kurtzhals, J. A. L., et al. (2022) · Apmis · doi:10.1111/apm.13259 · Cited by 9
“depleted from cell membranes resulting in reduced absorption of dietary iron, iron sequestration in cells, and reduced flow of iron into tissue fluids [4].”
BackgroundLópez, M., Quintero-Macías, L., Huerta, M., Rodríguez‐Hernández, A., Melnikov, V., Cárdenas, Y., Bricio‐Barrios, J. A., Sánchez-Pastor, E. A., Gamboa‐Domínguez, A., Leal, C. A., et al. (2022) · Molecules · doi:10.3390/molecules27227764 · Cited by 9
“IL-6 pathway activation can induce hepcidin synthesis [29], and increments in IL-6 levels have been correlated with elevated glycemia in diabetes [30].”
BackgroundPGC-1α Regulates Hepatic Hepcidin Expression and Iron Homeostasis in Response to inflammation
Qian, J., Chen, S., Huang, Y., Shi, X., & Liu, C. (2013) · Molecular Endocrinology · doi:10.1210/me.2012-1345 · Cited by 9
Iron deficiency without anaemia: Do not wait for the haemoglobin to drop?
Rattehalli, D., Pickard, L., Tselepis, C., Sharma, N., & Iqbal, T. H. (2013) · Health Policy and Technology · doi:10.1016/j.hlpt.2012.12.005 · Cited by 9
Allogeneic Transplantation, Fas Signaling, and Dysregulation of Hepcidin
Li, X., Xu, F., Karoopongse, E., Marcondes, A. M., Lee, K., Kowdley, K. V., Miao, C. H., Trobridge, G. D., Campbell, J. S., & Deeg, H. J. (2013) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2013.05.012 · Cited by 9
“However, FLIPL also mediates activation of NF-kB by recruiting adaptor proteins, such as Fas-associated death domain [23,34,35], and NF-kB potently promotes expression of IL-6 [18], which in turn is followed by STAT3 phosphorylation [36] and induction of hepcidin [37].”
BackgroundEffect of diquat-induced oxidative stress on iron metabolism in male Fischer-344 rats
Higuchi, M., Yoshikawa, Y., Orino, K., & Watanabe, K. (2011) · BioMetals · doi:10.1007/s10534-011-9471-0 · Cited by 9
“Infusion of IL-6 in human volunteers rapidly induces Hepc expression, leading to hypoferremia, whereas Hepc expression does not increase in IL-6 knock-out mice injected with turpentine, and these animals do not develop hypoferremia ( Nemeth et al. 2004a ).”
BackgroundCrosstalk between Erythropoiesis and Iron Metabolism
Rivella, S., Nemeth, E., & Miller, J. L. (2010) · Advances in Hematology · doi:10.1155/2010/317095 · Cited by 9
Self-citationMolecular analysis of Ceruloplasmin in a South African cohort presenting with oesophageal cancer
Strickland, N. J., Matsha, T. E., Erasmus, R., & Zaahl, M. G. (2011) · International Journal of Cancer · doi:10.1002/ijc.26418 · Cited by 10
Kanakdande, V. D., Patil, K. P., & Nayyar, A. S. (2015) · Contemporary Clinical Dentistry · doi:10.4103/0976-237x.161885 · Cited by 9
“[56] Previous studies indicated that IL‐6 mediates an increase in hepcidin levels and consequent hypoferremia during inflammation.[57] This also suggested that hepcidin could be the pathogenic mediator of ACD.”
Iron homeostasis after blood transfusion in stable preterm infants – an observational study
Herzlich, J., Litmanovitz, I., Regev, R. H., Bauer, S., Sirota, G. L., Steiner, Z., & Arnon, S. (2016) · Journal of Perinatal Medicine · doi:10.1515/jpm-2015-0361 · Cited by 9
An, P., Wang, H., Wu, Q., Guo, X., Wu, A., Zhang, Z., Zhang, D., Xu, X., Mao, Q., Shen, X., et al. (2015) · Scientific Reports · doi:10.1038/srep13106 · Cited by 10
Vokurka, M., Krijt, J., Vávrová, J., & Nečas, E. (2011) · Folia Biologica · doi:10.14712/fb2011057060248 · Cited by 9
“It is mainly IL-6, an acute-phase cytokine, which causes a significant increase of hepcidin and hypoferraemia (Nemeth et al., 2004a; Kemna et al., 2005).”
BackgroundSiltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma
Ferrario, A., Merli, M., Basilico, C., Maffioli, M., & Passamonti, F. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1288213 · Cited by 11
“IL-6 plays an important role in genesis of anemia of inflammation, in particular it has been demonstrated that induces the synthesis of hepcidin [45].”
BackgroundFukuda, T., Ishiyama, T., Katagiri, T., Ueda, K., Muramatsu, S., Hashimoto, M., Aki, A., Baba, D., Watanabe, K., & Tanaka, N. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.09.010 · Cited by 9
Prognostic associations of plasma hepcidin in women with early breast cancer
Jerzak, K. J., Lohmann, A. E., Ennis, M., Nemeth, E., Ganz, T., & Goodwin, P. J. (2020) · Breast Cancer Research and Treatment · doi:10.1007/s10549-020-05903-z · Cited by 9
Self-citationChandrakasan, S., Bakeer, N., Mo, J. Q., Cost, C. R., & Quinn, C. T. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.11.026 · Cited by 9
A New Wrinkle in the Fold: Hepcidin Links Inflammation to the Unfolded Protein Response
Domenico, I. D., & Kaplan, J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.005 · Cited by 9
“In hepatocytes, LPS and IL-6 lead to hepcidin transcription through the Stat family of transcription factors (Verga Falzacappa et al., 2007).”
BackgroundInfluentialCytotoxic Doses of Ketoconazole Affect Expression of a Subset of Hepatic Genes
Casley, W. L., Ogrodowczyk, C., Larocque, L., Jaentschke, B., LeBlanc-Westwood, C. A., Menzies, J. A., Whitehouse, L. W., Hefford, M. A., Aubin, R. A., Thorn, C. F., et al. (2007) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390701551407 · Cited by 9
“Hepcidin was proposed to be a peptide hormone at the interface of innate immunity and iron metabolism ( Nemeth et al, 2004 ; Ganz, 2006 ).”
BackgroundIron and Testosterone: Interplay and Clinical Implications
Gabrielsen, J. S. (2017) · Current Sexual Health Reports · doi:10.1007/s11930-017-0097-2 · Cited by 9
Abioye, A. I., Hughes, M. D., Sudfeld, C. R., Premji, Z. G., Aboud, S., Hamer, D. H., Roberts, D. J., Duggan, C., & Fawzi, W. W. (2022) · European Journal of Nutrition · doi:10.1007/s00394-022-03029-0 · Cited by 10
“Elevated hepcidin increases iron sequestration in the reticuloendothelial system [14, 16], and reduces iron absorption in the gastrointestinal tract, which reduce bioavailability of adequate iron stores, and limits the effectiveness of iron supplementation [17].”
BackgroundPino, J. M. V., Silva, V. F., Mônico‐Neto, M., Seva, D. C., Kato, M. Y., Alves, J., Pereira, G. C., Antunes, H. K. M., Galvão, T. D., Bitterncourt, L. R. A., et al. (2023) · International Journal of Endocrinology · doi:10.1155/2023/7625720 · Cited by 9
“Te data from the literature suggest that hepcidin expression can be increased by IL-6 signaling [23], but we did not observe signifcant correlation between IL-6 and hepcidin (rho� 0.”
BackgroundExercise-Associated Iron Deficiency
Goldstein, E. R. (2016) · Strength and conditioning journal · doi:10.1519/ssc.0000000000000202 · Cited by 12
“Interleukin-6 has been shown to be the main mediator of hepcidin production (31,38,43).”
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“A cytokine storm produced by SARS-COV-2 results from massive amounts of IL-6 expression which induces the production of hepcidin [49].”
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Self-citationCharacterization of erythroferrone structural domains relevant to its iron-regulatory function
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“, IL-6) (66), which in turn suppresses iron absorption from the gastrointestinal lumen.”
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Effects of Acute Dietary Iron Overload in Pigs (Sus scrofa) with Induced Type 2 Diabetes Mellitus
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“During inflammatory processes, Hpc is stimulated by IL-6, generating anemia of inflammatory response, during which a redistribution of Fe reserves mainly accumulate in macrophages is generated [42, 43].”
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Metadata
- Authors
- Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Rigshospitalet (DK)
- Corresponding author
- Ganz, Tomas
- Venue
- Journal of Clinical Investigation
- Published
- 2004-05-01
- Volume
- 113
- Issue
- 9
- Pages
- 1271-1276
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC398432
- OpenAlex
- W2132155262
- Cited by
- 2,650
- References
- 40
- Citations by year
- 2026: 100 · 2025: 97 · 2024: 93 · 2023: 117 · 2022: 115 · 2021: 145 · 2020: 134 · 2019: 130 · 2018: 130 · 2017: 141 · 2016: 103 · 2015: 135 · 2014: 132 · 2013: 140 · 2012: 137
- FWCI
- 55.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- David Geffen School of Medicine, University of California, Los Angeles
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- interleukin-6, hepcidin, iron regulation, inflammation, cytokine signaling, liver, iron regulatory hormone
- MeSH terms
- Anemia, Animals, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Inflammation, Iron, Kupffer Cells, Mice, Inbred C57BL, Monocytes, RNA, Messenger, Interleukin-6, Mice, Knockout, Iron Metabolism Disorders, Reverse Transcriptase Polymerase Chain Reaction, Hepatocytes, Antimicrobial Cationic Peptides, Mice, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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