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
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Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
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Iron metabolism in thalassemia and sickle cell disease
Mariani, R., Trombini, P., Matteo Pozzi, & Piperno, A. (2009) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2009.006 · Cited by 76
A review of anaemia of inflammatory disease in dogs and cats
Chikazawa, S., & Dunning, M. (2016) · Journal of Small Animal Practice · doi:10.1111/jsap.12498 · Cited by 83
Theurl, I., Fritsche, G., Ludwiczek, S., Garimorth, K., Bellmann-Weiler, R., & Weiss, G. (2005) · BioMetals · doi:10.1007/s10534-005-3710-1 · Cited by 72
Aguilar-Valles, A., Flores, C., & Luheshi, G. N. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010967 · Cited by 72
“The strongest evidence to date suggests that the pro-inflammatory cytokine IL-6, which is readily detectable in the circulation of infected individuals regardless of the pathogenic trigger, is the main circulating mediator of hepatic HAMP mRNA expression [19–22].”
BackgroundIL-22 Regulates Iron Availability In Vivo through the Induction of Hepcidin
Smith, C. S., Arvedson, T., Cooke, K. S., Dickmann, L. J., Forte, C. P., Li, H., Merriam, K. L., Perry, V. K., Tran, L., Rottman, J. B., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202716 · Cited by 81
Systemic Nonarticular Manifestations of Rheumatoid Arthritis: Focus on Inflammatory Mechanisms
Moreland, L. W., & Curtis, J. R. (2008) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2008.08.003 · Cited by 73
Fillebeen, C., Wilkinson, N., Charlebois, E., Katsarou, A., Wagner, J., & Pantopoulos, K. (2018) · Blood · doi:10.1182/blood-2018-03-841197 · Cited by 73
The pathology of bone marrow failure
Leguit, R. J., & van den Tweel, J. G. (2010) · Histopathology · doi:10.1111/j.1365-2559.2010.03612.x · Cited by 72
Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia
Cheng, P., Jiao, X., Wang, X., Lin, J.-H., & Cai, Y. (2010) · Clinical and Experimental Medicine · doi:10.1007/s10238-010-0102-9 · Cited by 74
Mutual interaction between iron homeostasis and obesity pathogenesis
Nikonorov, A. А., Геннадиевна, С. М., Tinkov, A. A., & Skalny, A. V. (2014) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2014.05.005 · Cited by 77
“[49] Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.”
BackgroundInfluentialAge-Related Changes and Sex-Related Differences in Brain Iron Metabolism
Kezele, T. G., & Ćurko‐Cofek, B. (2020) · Nutrients · doi:10.3390/nu12092601 · Cited by 78
“The increased hepcidin synthesis causes iron sequestration in macrophages and decreases iron availability in tissues, limiting the growth of microbes [70] and causing the characteristic hypoferremia and eventually anemia of inflammation [93,95].”
BackgroundInfluentialRole of hepatic iron in non‐alcoholic steatohepatitis
Sumida, Y., Yoshikawa, T., & Okanoue, T. (2008) · Hepatology Research · doi:10.1111/j.1872-034x.2008.00442.x · Cited by 71
Shaler, C. R., Parco, A. A., Elhenawy, W., Dourka, J., Jury, J., Verdu, E. F., & Coombes, B. K. (2021) · Nature Communications · doi:10.1038/s41467-021-26992-4 · Cited by 74
Chou, D. B., Sworder, B. J., Bouladoux, N. J., Roy, C. N., Uchida, A. M., Grigg, M. E., Robey, P. G., & Belkaid, Y. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.1011527 · Cited by 71
“Relatively recent literature has established a critical function for IL-6, which can act through hepcidin to reduce iron availability and restrict erythropoiesis [5–9].”
BackgroundEmerging Regulatory Role of Nrf2 in Iron, Heme, and Hemoglobin Metabolism in Physiology and Disease
Kasai, S., Mimura, J., Ozaki, T., & Itoh, K. (2018) · Frontiers in Veterinary Science · doi:10.3389/fvets.2018.00242 · Cited by 73
“Furthermore, hepcidin is increased by the inflammatory cytokine, such as IL-6 in the liver and degrades FPN1 in macrophages (28).”
BackgroundInsenser, M. R., Martínez-García, M. Á., Montes, R., San‐Millán, J. L., & Escobar-Morreale, H. F. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0220 · Cited by 71
“In chronic inflammatory conditions, cytokines such as IL-6 enhance the synthesis of hepcidin (33), the predominant negative regulator of iron absorption in the small intestine and iron release from macrophages, leading to the anemia of chronic disorders in severe cases by limiting the amount of iron available for eryt…”
BackgroundArmitage, A. E., & Moretti, D. (2019) · Pharmaceuticals · doi:10.3390/ph12020059 · Cited by 76
Hashizume, M., Uchiyama, Y., Horai, N., Tomosugi, N., & Mihara, M. (2010) · Rheumatology International · doi:10.1007/s00296-009-1075-4 · Cited by 70
“(2) IL-6 induces hepcidin production in liver cells [11].”
BackgroundHeme Oxygenase-1 and Iron in Liver Inflammation: A Complex Alliance
Immenschuh, S., Baumgart‐Vogt, E., & Mueller, S. (2010) · Current Drug Targets · doi:10.2174/1389450111009011541 · Cited by 71
“These mechanisms include interleukin (IL)-6-mediated induction of hepcidin [32, 46], which inhibits iron efflux from macrophages and intestinal enterocytes by binding to and promoting the degradation of the transporter FPN1 (synonymous with IREG1 or MTP1)(Figs.”
BackgroundInfluentialPrzybyszewska, J., & Żekanowska, E. (2014) · Gastroenterology Review · doi:10.5114/pg.2014.45102 · Cited by 70
Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions
Natalucci, V., Virgili, E., Calcagnoli, F., Valli, G., Agostini, D., Zeppa, S. D., Barbieri, E., & Emili, R. (2021) · Nutrients · doi:10.3390/nu13020482 · Cited by 72
Iron Homeostasis and Disorders in Dogs and Cats: A Review
McCown, J. L., & Specht, A. J. (2011) · Journal of the American Animal Hospital Association · doi:10.5326/jaaha-ms-5553 · Cited by 73
“As discussed previously, this results in inhibition of duodenal iron absorption and decreases iron release from stores in macrophages and hepatocytes.(28) IFN-g, LPS, and TNF-a up-regulate DMT1 expression on macrophages with a resultant increased uptake of iron into these cells.”
BackgroundChalhoub, S., Langston, C. E., & Eatroff, A. E. (2011) · Journal of Feline Medicine and Surgery · doi:10.1016/j.jfms.2011.07.016 · Cited by 83
Epithelial Transport in Inflammatory Bowel Diseases
Ghishan, F. K., & Kiela, P. R. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000029 · Cited by 69
“results in a defect in the efflux of iron from the cell (including enterocytes and macrophages) to the systemic circulation.(132) Experimental induction of hepcidin expression by turpentine”
BackgroundIs Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?
Pasini, A. M. F., Stranieri, C., Girelli, D., Busti, F., & Cominacini, L. (2021) · Antioxidants · doi:10.3390/antiox10111677 · Cited by 72
“In response to microbial or viral molecules, multiple inflammatory cytokines and, in particular, interleukin-6 (IL-6) are released by cells of the immune system and alter systemic iron metabolism [74].”
BackgroundPaesano, R., Berlutti, F., Pietropaoli, M., Goolsbee, W., Pacifici, E., & Valenti, P. (2010) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201002300220 · Cited by 69
Iron metabolism: State of the art
Daher, R., & Karim, Z. (2017) · Transfusion Clinique et Biologique · doi:10.1016/j.tracli.2017.06.015 · Cited by 69
From bench to bedside and back again: translational research in autoinflammation
Holzinger, D., Kessel, C., Omenetti, A., & Gattorno, M. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.79 · Cited by 69
The value of blocking IL-6 outside of rheumatoid arthritis: current perspective
Murakami, M., & Nishimoto, N. (2011) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e3283456797 · Cited by 82
Paesano, R., Berlutti, F., Pietropaoli, M., Pantanella, F., Pacifici, E., Goolsbee, W., & Valenti, P. (2010) · BioMetals · doi:10.1007/s10534-010-9335-z · Cited by 69
“Even if the molecular mechanisms of hepcidin regulation by iron and anemia are still unclear (Nemeth and Ganz 2006b), it is well known that iron loading and Interleukin-6 (IL-6) increase hepcidin gene transcription in hepatocytes ( Nemeth et al. 2004b ).”
BackgroundInfluentialMaternal Obesity Affects Inflammatory and Iron Indices in Umbilical Cord Blood
Dosch, N. C., Guslits, E., Weber, M. B., Murray, S. E., Ha, B., Coe, C. L., Auger, A. P., & Kling, P. J. (2016) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2016.02.023 · Cited by 69
Iron and iron-related proteins in COVID-19
Suriawinata, E., & Mehta, K. J. (2022) · Clinical and Experimental Medicine · doi:10.1007/s10238-022-00851-y · Cited by 69
“Hepcidin is induced by infection/inflammation, specifically by IL6 via the JAK/STAT signaling pathway [108].”
BackgroundEffect of iron liposomes on anemia of inflammation
Li, Y., Geng, L., Ge, L., Yu, P., Duan, X., Chen, J., & Chang, Y. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.06.078 · Cited by 68
“Recently, research on the pathogenesis of AI has focused on the role of hepcidin, a 25-amino acid peptide synthesized in the liver and triggered by inflammatory stimulators such as interleukin-6 (Nemeth et al., 2004).”
BackgroundThe Utility of Serum Hepcidin as a Biomarker for Late-Onset Neonatal Sepsis
Wu, T.-W., Tabangin, M. E., Kusano, R., Ma, Y., Ridsdale, R. A., & Akinbi, H. T. (2012) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2012.06.010 · Cited by 68
Waalen, J., von Löhneysen, K., Lee, P. L., Xu, X., & Friedman, J. S. (2011) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2011.01631.x · Cited by 68
“The gene encoding hepcidin, HAMP, is regulated in part by inflammatory cytokines and has been shown to be responsive to IL6 levels (17).”
BackgroundCeliac Disease Is Associated with Restless Legs Syndrome
Weinstock, L. B., Walters, A. S., Mullin, G. E., & Duntley, S. P. (2009) · Digestive Diseases and Sciences · doi:10.1007/s10620-009-0943-9 · Cited by 68
“Interleukin-6 upregulates the levels of hepcidin, a liver-produced hormone that controls plasma iron levels by regulating absorption of dietary iron from the intestine [34,35].”
BackgroundSirukumab for rheumatoid arthritis: the phase III SIRROUND-D study
Takeuchi, T., Thorne, C., Karpouzas, G. A., Sheng, S., Xu, W., Rao, R., Fei, K., Hsu, B. L., & Tak, P. P. (2017) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2017-211328 · Cited by 68
Targeting interleukin-6 for noninfectious uveitis
Lin, P. (2015) · Clinical ophthalmology · doi:10.2147/opth.s68595 · Cited by 68
“They also include hepcidin which blocks the action of ferroportin, an iron transporter in the gut, thus contributing to anemia of chronic inflammatory disease.(11) Importantly, IL-6 can induce production of vascular endothelial growth factor, resulting in the neovascular process that can sometimes accompany inflammati…”
Effects of Interleukin-1β Inhibition on Incident Anemia
Vallurupalli, M., MacFadyen, J. G., Glynn, R. J., Thuren, T. Y., Libby, P., Berliner, N., & Ridker, P. M. (2020) · Annals of Internal Medicine · doi:10.7326/m19-2945 · Cited by 68
“This iron regulatory mediator rises in iron overload and inflammatory states (4, 5).”
BackgroundMoliner, P., Jankowska, E. A., van Veldhuisen, D. J., Farre, N., Rozentryt, P., Enjuanes, C., Polonski, L., Meroño, O., Voors, A. A., Ponikowski, P., et al. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.04.110 · Cited by 67
Kupffer cells and macrophages are not required for hepatic hepcidin activation during iron overload†
Montosi, G., Corradini, E., Garuti, C., Barelli, S., Recalcati, S., Cairo, G., Valli, L., Pignatti, E., Vecchi, C., Ferrara, F., et al. (2005) · Hepatology · doi:10.1002/hep.20620 · Cited by 67
Frame, J. M., Kubaczka, C., Long, T. L., Esain, V., Soto, R. A., Hachimi, M., Jing, R., Shwartz, A., Goessling, W., Daley, G. Q., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.07.015 · Cited by 68
“This effect may be due to amplified production of downstream cytokines, including IL6 (Nemeth et al., 2004; Zhao et al., 2014).”
BackgroundInfluentialPietrangelo, A., & Trautwein, C. (2004) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep0019 · Cited by 69
“In both mice and humans, IL-6, which is probably produced by KUPFFER CELLS , acts directly on hepatocytes to stimulate hepcidin production”
BackgroundAkın, F., Köse, N., Ayça, B., Katkat, F., Duran, M., Uysal, O. K., & Arınç, H. (2012) · Angiology · doi:10.1177/0003319712461931 · Cited by 67
“Inflammation might contribute to an increased RDW by inhibiting erythropoietin-induced erythrocyte maturation(18) and impairing iron metabolism.(19) In addition, in the early phase of AMI Table 2.”
BackgroundInterleukin-6 contributes to hepcidin mRNA increase in response to exercise
Banzet, S., Sanchez, H., Chapot, R., Bigard, X. A., Vaulont, S., & Koulmann, N. (2012) · Cytokine · doi:10.1016/j.cyto.2012.01.006 · Cited by 67
Hashizume, M., Tan, S., Takano, J., Ohsawa, K., Hasada, I., Hanasaki, A., Ito, I., Mihara, M., & Nishida, K. (2014) · International Reviews of Immunology · doi:10.3109/08830185.2014.938325 · Cited by 68
“In this regard, IL-6 is known to induce hepcidin production in liver cells [48].”
BackgroundIron homeostasis: new players, newer insights
Edison, E. S., Bajel, A. R., & Chandy, M. (2008) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2008.01143.x · Cited by 71
“Hepcidin expression is induced by lipopolysaccharide and interleukin-6 and is inhibited by TNF-a (93).”
BackgroundKong, W.-N., Gao, G., & Chang, Y.-Z. (2014) · Cell & Bioscience · doi:10.1186/2045-3701-4-19 · Cited by 71
“Hepcidin synthesis was markedly induced by infection and inflammation [51,60], and IL-6 itself is sufficient to induce hepcidin expression during inflammation [61].”
BackgroundCell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19
Li, X., Zhang, Z., Wang, Z., Gutiérrez-Castrellón, P., & Shi, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01043-6 · Cited by 67
Dunne, J. R., Riddle, M. S., Danko, J., Hayden, R., & Petersen, K. (2006) · The American Surgeon · doi:10.1177/000313480607200709 · Cited by 67
Howard, C. T., McKakpo, U. S., Quakyi, I. A., Bosompem, K. M., Addison, E. A., Sun, K., Sullivan, D., & Semba, R. D. (2007) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2007.77.623 · Cited by 66
“implicated in the modulation of hepcidin expression include hypoxia(4) and inflammation.(9) In malaria, the destruction of parasitized and normal erythrocytes, as well as ineffective erythropoiesis contribute almost equally to anemia, but recent data suggest that these mechanisms alone or in combination do not adequat…”
BackgroundTargeting the interleukin‐6 receptor: A new treatment for systemic juvenile idiopathic arthritis?
Benedetti, F. D., & Martini, A. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20946 · Cited by 66
The Role of Hepcidin in Iron Homeostasis and Anemia in Hemodialysis Patients
Eleftheriadis, T., Liakopoulos, V., Antoniadi, G., Kartsios, C., & Stefanidis, I. (2009) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2008.00532.x · Cited by 66
“Healthy humans respond to IL-6 infusion with hepcidin production and hypoferremia within hours (53).”
BackgroundResultInfluentialFord, B. A., Eby, C. S., Scott, M. G., & Coyne, D. W. (2010) · Kidney International · doi:10.1038/ki.2010.254 · Cited by 67
Urrutia, P. J., Hirsch, É. C., González-Billault, C. E., & Núñez, M. T. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14005 · Cited by 68
The bone morphogenetic protein–hepcidin axis as a therapeutic target in inflammatory bowel disease
Wang, L., Trebicka, E., Fu, Y., Ellenbogen, S., Hong, C. C., Babitt, J. L., Lin, H. Y.-F., & Cherayil, B. J. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21675 · Cited by 66
“The decrease in ferroportin expression that results from elevated hepcidin levels would block entry of iron into the circulation, with consequent impairment of erythropoiesis.(3,16) Furthermore, since intestinal absorption of iron is inhibited by the hepcidin-mediated downregulation of ferroportin on enterocytes, the…”
BackgroundCutone, A., Lepanto, M. S., Rosa, L., Scotti, M. J., Rossi, A., Ranucci, S., Fino, I. D., Bragonzi, A., Valenti, P., Musci, G., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092128 · Cited by 69
High‐sensitive radioimmunoassay for human serum hepcidin
Grebenchtchikov, N. I., Geurts-Moespot, A. J., Kroot, J. J., den Heijer, M., Tjalsma, H., Swinkels, D. W., & Sweep, F. C. G. J. (2009) · British Journal of Haematology · doi:10.1111/j.1365-2141.2009.07758.x · Cited by 65
“Hepcidin-25 leads to internalisation and degradation of the iron exporter ferroportin, which is present on the cell surface of macrophages and enterocytes (Nemeth et al, 2004a; De Domenico et al, 2008a).”
BackgroundMethodThe Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1
Hull, T. D., Agarwal, A., & George, J. F. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5673 · Cited by 65
“However, when HO-1-deficient macrophages are treated with oxLDL, generation of ROS is amplified and secretion of pro-inflammatory IL-6, MCP-1, and the IL-8 homologue, KC is increased (128).”
BackgroundInfluentialOptimal serum ferritin level range: iron status measure and inflammatory biomarker
DePalma, R. G., Hayes, V. W., & O’Leary, T. J. (2021) · Metallomics · doi:10.1093/mtomcs/mfab030 · Cited by 65
Lim, D., Kim, K. S., Jeong, J.-H., Marques, O., kim, H.-J., Song, M., Lee, T.-H., Kim, J. I., Choi, H.-S., Min, J.-J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04446-8 · Cited by 64
Hepcidin expression in human airway epithelial cells is regulated by interferon-γ
Frazier, M. D., Mamo, L. B., Ghio, A. J., & Turi, J. L. (2011) · Respiratory Research · doi:10.1186/1465-9921-12-100 · Cited by 64
Effects of an acute exercise bout on serum hepcidin levels
Domínguez, R., Sánchez-Oliver, A., Mata-Ordoñez, F., Feria-Madueño, A., Grimaldi-Puyana, M., López-Samanes, Á., & Pérez-López, A. (2018) · Nutrients · doi:10.3390/nu10020209 · Cited by 64
“Consequently, instead of the post-exercise increase, the chronic elevation of IL-6 at baseline may be interpreted as a pro-inflammatory signal that may activate the inflammatory-induced expression of hepcidin observed in vitro and in vivo [46,119].”
BackgroundWhat can we learn from ineffective erythropoiesis in thalassemia?
Oikonomidou, P. R., & Rivella, S. (2017) · Blood Reviews · doi:10.1016/j.blre.2017.10.001 · Cited by 67
Mycobacterium tuberculosis components stimulate production of the antimicrobial peptide hepcidin
Sow, F. B., Nandakumar, S., Velu, V., Kellar, K. L., Schlesinger, L. S., Amara, R. R., Lafuse, W. P., Shinnick, T. M., & Sable, S. B. (2011) · Tuberculosis · doi:10.1016/j.tube.2011.03.003 · Cited by 64
Serum hepcidin level and erythropoietic activity after hematopoietic stem cell transplantation
Kanda, J., Mizumoto, C., Kawabata, H., Tsuchida, H., Tomosugi, N., Matsuo, K., & Uchiyama, T. (2008) · Haematologica · doi:10.3324/haematol.12399 · Cited by 64
Wagner, M., Alam, A., Zimmermann, J., Rauh, K., Batzner, A., Raff, U., Wanner, C., & Schramm, L. (2011) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.00380111 · Cited by 65
Iron transport & homeostasis mechanisms: their role in health & disease.
Nadadur, S. S., Srirama, K., & Mudipalli, A. (2008) · PubMed · Cited by 64
Lewies, A., Wentzel, J. F., Jacobs, G., & Plessis, D. (2015) · Molecules · doi:10.3390/molecules200815392 · Cited by 67
“in hypoferremia of inflammation which increases the microbial resistance of host cells [117].”
BackgroundGao, W., Wang, W., Liu, G., Zhang, J., Yang, J. M., & Deng, Z. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0342-z · Cited by 64
“Iron homeostasis might be perturbed after glial cells activated during neuroinflammation (Lee et al. 2004; Nemeth et al. 2004).”
BackgroundJasiecki, J., Targońska, M., & Wasąg, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042033 · Cited by 67
Regulation of Iron Homeostasis and Related Diseases
Li, Y., Huang, X., Wang, J., Huang, R., & Wan, D. (2020) · Mediators of Inflammation · doi:10.1155/2020/6062094 · Cited by 66
“Interleukin-6 (IL-6) is one kind of cytokine that regulates the transcription of hepcidin [76].”
BackgroundDevelopment of a novel immunoassay for the iron regulatory peptide hepcidin
Busbridge, M., Griffiths, C., Ashby, D. R., Gale, D. P., Jayantha, A., Sanwaiya, A., & Chapman, R. (2009) · British Journal of Biomedical Science · doi:10.1080/09674845.2009.11730263 · Cited by 63
Alonso, D. P., Ferreira, A. F. B., Ribolla, P. E. M., Santos, I. K. F. D. M., Cruz, M. D. S. P. E., Carvalho, F. A. D. A., Abatepaulo, A. R. R., Costa, D. L., Werneck, G. L., Farias, T. J. C., et al. (2007) · The Journal of Infectious Diseases · doi:10.1086/512683 · Cited by 63
“TNF-a causes anemia in infections by inhibiting production of erythropoietin [28] and, through activation of macrophages, by promoting erythrophagocytosis [29]; hypoferremia of infection is caused by IL6 and hepcidin [30].”
BackgroundMolecular basis of iron-loading disorders
Darshan, D., Frazer, D. M., & Anderson, G. J. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001687 · Cited by 63
Christiansen, H., Sheikh, N., Saile, B., Reuter, F., Rave‐Fränk, M., Hermann, R. M., Dudás, J., Hille, A., Hess, C. F., & Ramadori, G. P. (2007) · Radiology · doi:10.1148/radiol.2421060083 · Cited by 64
Nieuwenhuizen, L., Schutgens, R. E. G., van Asbeck, B. S., Wenting, M. J. G., van Veghel, K., Roosendaal, G., Biesma, D. H., & Lafeber, F. P. J. G. (2013) · Haemophilia · doi:10.1111/hae.12208 · Cited by 66
Kamai, T., Tomosugi, N., Abe, H., Arai, K., & Yoshida, K. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-270 · Cited by 65
“Production of hepcidin-25 is induced in the liver by IL-6 [19].”
BackgroundVela, D. (2018) · Molecular Medicine · doi:10.1186/s10020-018-0008-7 · Cited by 65
“Its complex with hepcidin induces FPN degradation inside cells (Nemeth et al. 2004).”
BackgroundInfluentialSkarpańska-Stejnborn, A., Basta, P., Trzeciak, J., & Pilaczyńska-Szczȩśniak, Ł. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-014-3018-3 · Cited by 63
“According to Nemeth et al. (2004), impaired hemoglobin synthesis can result from a transient increase in hepcidin activity, which causes rapidly decreasing plasma iron levels and resultant anemia.”
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Smoking-induced iron dysregulation in the lung
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“Hepcidin expression and release is induced by increased serum iron, by bone morphogenic protein (BMP) signaling [50] and by a number of pro-inflammatory cytokines including IL-6 and IL-22 [51].”
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“This effect may be attributable to inhibition of production of hepcidin (an iron-regulatory peptide secreted by liver cells) [30-33] and/or to the recovery of erythropoietin signal transduction.”
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Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores
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“Molecularly, it binds to ferroportin (FPN), inducing its internalization, ubiquitinylation, and consecutive degradation of FPN in the lysoproteasome (77), while iron is retained within the cells (81, 83).”
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Uncoupled iron homeostasis in type 2 diabetes mellitus
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Modulation of iron homeostasis with hepcidin ameliorates spontaneous murine lupus nephritis
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“IL-6) are also important factors in hepcidin regulation [32].”
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“C-reactive protein (mg/L) 3 (0-7) 3 (0-7) 3 (0-6) 5 (1-8) 0.”
Recent advances in understanding haemochromatosis: a transition state
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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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