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
23 Own result · 13 No full text of the sources · 13 Own interpretation · 6 Supported · 3 Partly supported · 1 Couldn’t confirm · 1 No basis given · 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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)
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- 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)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- 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)
plain- Asserted: passes — The authors put it forward as true.
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- 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”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Anti-TNFα Ab's had no detectable effect in either experiment”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Hep3B hepcidin mRNA, however, markedly increased after exposure to M-LPS”
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
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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”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“in IL-6 KO mice hepcidin mRNA increased ninefold”
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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)
boosteddirect- Asserted: passes — The authors put it forward as true.
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It 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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”
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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It 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”
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
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It 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”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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”
plainn = 13- Asserted: passes — The authors put it forward as true.
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It 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”
plaindirectn = 5 ·- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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.”
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably 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”
hedgeddirectn = 5- Asserted: passes — The authors put it forward as true.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“However, hepcidin is overexpressed in inflammatory disease and is an early inflammatory marker [245,341-345].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [342]
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
“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
“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].”
The cited source says what the claim attributes to it.
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]
The 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
“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
“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
“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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Six healthy volunteers collected first morning urine for 9 days.”
“Five subjects took 65 mg of iron (as ferrous sulfate) for 3 days, and their urinary hepcidin was monitored before, during, and after iron supplementation.”
Citations
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Weiss, G., & Goodnough, L. T. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041809 · Cited by 3,800
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
Self-citationAndrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544
Self-citationHepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
Nemeth, E., Valore, E. V., Territo, M., Schiller, G., Lichtenstein, A., & Ganz, T. (2003) · Blood · doi:10.1182/blood-2002-10-3235 · Cited by 1,417
Self-citationLEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity
Krause, A., Neitz, S., Mägert, H.-J., Schulz, A., Forssmann, W.-G., Schulz-Knappe, P., & Adermann, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01920-7 · Cited by 1,324
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282
Research works printed but not linked: 2
- Means, 1999, Int. J. Hematol., 70, 7
- Barille, 2000, Eur. Cytokine Netw., 11, 546
Cited by
Sorted by citations
Items 1,001–1,100 of 2,683
Molecular perspective of iron uptake, related diseases, and treatments
Shokrgozar, N., & Golafshan, H. (2019) · Blood Research · doi:10.5045/br.2019.54.1.10 · Cited by 37
He, J., Han, S., Li, X., Wang, Q., Cui, Y., Chen, Y., Gao, H., Huang, L., & Yang, S. (2019) · Molecules · doi:10.3390/molecules24244502 · Cited by 36
Hoeger, J., Simon, T.-P., Doemming, S., Thiele, C., Marx, G., Schuerholz, T., & Haase, H. (2015) · BioMetals · doi:10.1007/s10534-015-9858-4 · Cited by 36
Nunes, A. R., & Tata, M. (2017) · Revista Portuguesa de Pneumologia · doi:10.1016/j.rppnen.2016.12.005 · Cited by 40
Mouse Models of Anemia of Cancer
Kim, A., Rivera, S., Shprung, D., Limbrick, D., Gabayan, V., Nemeth, E., & Ganz, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093283 · Cited by 35
Self-citationMcCranor, B. J., Langdon, J., Prince, O. D., Femnou, L. K., Berger, A. E., Cheadle, C., Civin, C. I., Kim, A., Rivera, S., Ganz, T., et al. (2013) · Haematologica · doi:10.3324/haematol.2013.087114 · Cited by 35
“We did observe an increase in Id1 expression, which is sensitive to increased iron stores46 and IL-6.”
BackgroundSelf-citationSerum Hepcidin-20 is Elevated during the Acute Phase of Myocardial Infarction
Suzuki, H., Toba, K., Kato, K., Ozawa, T., Tomosugi, N., Higuchi, M., Kusuyama, T., Iso, Y., Kobayashi, N., Yokoyama, S.-I., et al. (2009) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.218.93 · Cited by 38
Chauhan, A., Midha, S., Kumar, R., Meena, R. K., Singh, P., Jha, S. K., & Kuanr, B. K. (2021) · Biomaterials Science · doi:10.1039/d0bm01705a · Cited by 35
Ciccarelli, B. T., Patterson, C. J., Hunter, Z. R., Hanzis, C., Ioakimidis, L., Manning, R. J., Yang, G., Xu, L., Zhou, Y., Sun, J., et al. (2011) · Clinical Lymphoma Myeloma & Leukemia · doi:10.3816/clml.2011.n.038 · Cited by 35
Gaillard, S., Bock, A. H., Carrera, F., Eckardt, K., Wyck, D. B. V., Bansal, S. S., Cronin, M., Meier, Y., Larroque, S., Roger, S. D., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157063 · Cited by 35
“An important regulator of hepcidin is inflammation, which stimulates production of hepcidin [3, 12], and chronic inflammation becomes most prominent as renal function declines [28].”
BackgroundKartikasari, A. E. R., Roelofs, R., Schaeps, R. M. J., Kemna, E., Peters, W. H. M., Swinkels, D. W., & Tjalsma, H. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2008.08.004 · Cited by 35
“During inflammation and systemic infection, IL-6 promotes hepcidin synthesis [7,8,14] utilizing signal transducers and activators of transcription-3 (STAT-3) as the transcription initiating factor [15–17].”
BackgroundCloning, sequencing and expression analysis of the equine hepcidin gene by real-time PCR
Oliveira-Filho, J. P., Badial, P. R., da Cunha, P. H. J., Cruz, T. F., Araújo, J. P., Divers, T. J., Winand, N. J., & Borges, A. S. (2009) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2009.10.027 · Cited by 35
“2, GeneID: 100050728; HEPC, hepcidin (Bos taurus), BC_111658.”
BackgroundMethodInfluentialIron Homeostasis during Cystic Fibrosis Pulmonary Exacerbation
Gifford, A. H., Moulton, L. A., Dorman, D. B., Olbina, G., Westerman, M. E., Parker, H. W., Stanton, B. A., & O’Toole, G. A. (2012) · Clinical and Translational Science · doi:10.1111/j.1752-8062.2012.00417.x · Cited by 35
Pelucchi, S., Mariani, R., Trombini, P., Coletti, S., Pozzi, M., Paolini, V., Barisani, D., & Piperno, A. (2009) · Haematologica · doi:10.3324/haematol.13576 · Cited by 35
“haematologica | 2009; 94(2) | 279 | ferrous sulfate, indicating a rapid hepatic response to iron.(13,20) By contrast, patients with HFE-HH have a decreased hepcidin response to oral iron.”
BackgroundAnemia of Inflammation Is Related to Cognitive Impairment among Children in Leyte, The Philippines
Olson‐Chen, C., Acosta, L. P., Hochberg, N. S., Olveda, R. M., Jiz, M., McGarvey, S. T., Kurtis, J. D., Bellinger, D. C., & Friedman, J. F. (2009) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000533 · Cited by 35
“Hepcidin, an acute phase protein induced by interleukin-6, has been proposed as the link between inflammatory disorders and AI [3,4].”
BackgroundLarvie, D. Y., Doherty, J., Donati, G. L., & Armah, S. M. (2019) · Antioxidants · doi:10.3390/antiox8100463 · Cited by 35
“due to its antimicrobial properties [9,10].”
Min, K.-S., Iwata, N., Tetsutikawahara, N., Onosaka, S., & Tanaka, K. (2008) · Toxicology Letters · doi:10.1016/j.toxlet.2008.04.001 · Cited by 35
Hemojuvelin: The Hepcidin Story Continues
Małyszko, J. (2009) · Kidney & Blood Pressure Research · doi:10.1159/000208988 · Cited by 35
“found that both hepcidin and HJV in mice were transcriptionally regulated during inflammation. However, TNF-α, not IL-6, caused HJV downregulation by LPS. In studies done in cultured human hepatocytes, HJV was a negative regulator of hepcidin mRNA expression. These data are in contrast to the previously published pape…”
ResultInfluence of post-exercise hypoxic exposure on hepcidin response in athletes
Badenhorst, C. E., DAWSON, B. T., Goodman, C., Sim, M., Cox, G. R., Gore, C. J., Tjalsma, H., Swinkels, D. W., & Peeling, P. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-014-2829-6 · Cited by 35
“…Endocrine and Metabolic Diseases, radboud University Medical centre, 6500 HB nijmegen, the netherlands 1 3 Hp Haptoglobin Hp-Hb Haptoglobin–Hemoglobin complex Hr Heart rate HYP Hypoxic/simulated altitude trial Il-6 Interleukin-6 lSD least significant difference mrnA Messenger rnA nOrM control…”
BackgroundInfluentialErythropoietic drive is the strongest predictor of hepcidin level in adults with sickle cell disease
Karafin, M. S., Koch, K. L., Rankin, A. B., Nischik, D., Rahhal, G., Simpson, P. M., & Field, J. J. (2015) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2015.07.010 · Cited by 36
Animal Models of Normal and Disturbed Iron and Copper Metabolism
Wang, X., Garrick, M. D., & Collins, J. F. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz172 · Cited by 35
“Transactivation of the hepcidin antimicrobial peptide gene (HAMP; encoding the iron-regulatory hormone hepcidin) in hepatocytes by proinflammatory cytokines (e.g., IL-6) leads to increases in circulating concentrations of the hormone.”
BackgroundInfluentialAbsolute and functional iron deficiency: Biomarkers, impact on immune system, and therapy
Iriarte‐Gahete, M., Tarancón‐Díez, L., Garrido‐Rodríguez, V., Leal, M., & Pacheco, Y. M. (2024) · Blood Reviews · doi:10.1016/j.blre.2024.101227 · Cited by 39
Li, G., Shi, S., Tan, J., He, L., Liu, Q., Fěng, F., Fu, H., Zhong, M., Mai, Z., Sun, R., et al. (2024) · Advanced Science · doi:10.1002/advs.202309464 · Cited by 35
Zughaier, S. M., Stauffer, B. B., & McCarty, N. A. (2014) · Journal of Immunology Research · doi:10.1155/2014/140728 · Cited by 34
“cytokine that plays a significant role in systemic iron metabolism by directly inducing the expression of hepcidin, the master iron-regulating hormone [8].”
BackgroundInfluentialClassical and intermediate monocytes scavenge non-transferrin-bound iron and damaged erythrocytes
Haschka, D., Petzer, V., Kocher, F., Tschurtschenthaler, C., Schaefer, B., Seifert, M., Sopper, S., Sonnweber, T., Feistritzer, C., Arvedson, T. L., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.98867 · Cited by 34
The investigation and treatment of secondary anaemia
Davis, S. L., & Littlewood, T. J. (2011) · Blood Reviews · doi:10.1016/j.blre.2011.10.003 · Cited by 34
Szekanecz, Z., Szántó, S., Szabó, Z., Váncsa, A., Szamosi, S., Bodnár, N., & Szűcs, G. (2010) · Autoimmunity Reviews · doi:10.1016/j.autrev.2010.07.011 · Cited by 34
Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney disease
Ferrari, P., Mallon, D., Trinder, D., & Olynyk, J. K. (2009) · Nephrology · doi:10.1111/j.1440-1797.2009.01203.x · Cited by 35
Low transferrin levels predict heightened inflammation in patients with COVID-19: New insights
Claise, C., Saleh, J., Rezek, M., Vaulont, S., Peyssonnaux, C., & Edeas, M. A. (2021) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2021.12.340 · Cited by 34
Troadec, M., Lainé, F., Daniel, V., Rochcongar, P., Ropert, M., Cabillic, F., Perrin, M., Morçet, J., Loréal, O., Olbina, G., et al. (2009) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1031-8 · Cited by 34
“IL-6 is an inXammatory signal which induces the synthesis of the iron regulatory hormone hepcidin ( Nemeth et al. 2003, 2004 ), resulting in hypoferremia (Nemeth et al. 2004) and increased iron storage within the reticuloendothelial system (Nicolas et al. 2002).”
BackgroundSelf-citationTransition Metal Homeostasis in Streptococcus pyogenes and Streptococcus pneumoniae
Turner, A. G., Ong, C. Y., Walker, M. J., Djoko, K. Y., & McEwan, A. G. (2017) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/bs.ampbs.2017.01.002 · Cited by 35
de Farias, C. C., Maes, M. H. J., Bonifácio, K. L., Matsumoto, A. K., Bortolasci, C. C., Souza-Nogueira, A., Brinholi, F. F., Morimoto, H. K., de Melo, L. B., Moreira, E. G., et al. (2017) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527316666170223161004 · Cited by 34
Hazlett, H. F., Hampton, T. H., Aridgides, D. S., Armstrong, D. A., Dessaint, J. A., Mellinger, D., Nymon, A. B., & Ashare, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-67729-5 · Cited by 37
Occurrence of Nonceliac Gluten Sensitivity in Patients with Allergic Disease
Massari, S., Liso, M., Santis, L. D., Mazzei, F., Carlone, A., Mauro, S., Musca, F., Bozzetti, M. P., & Minelli, M. (2011) · International Archives of Allergy and Immunology · doi:10.1159/000321196 · Cited by 34
“The majority of studies have focused on micronutrient deficiencies as the cause of anemia in individuals with CD; in our study group, this hypothesis appears inadequate. In fact, in our analysis only 60p of the anemic NCGSE patients had anemia with iron deficiency. The remaining 40p presented a normal or high level of…”
BackgroundSimavlı, S. A., Uysal, A., Uysal, S., & Turhan, N. Ö. (2013) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2013.804054 · Cited by 34
“Nemeth et al. noted that, ‘‘In vitro, the addition of IL-6neutralizing Ab’s to hepatocyte culture completely ablated the hepcidin increase induced by LPS or LPS-stimulated macrophages.”
BackgroundInfluentialInfluence of DMT1 and iron status on inflammatory responses in the lung
Kim, J., Molina, R. M., Donaghey, T. C., Buckett, P. D., Brain, J. D., & Wessling‐Resnick, M. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00343.2010 · Cited by 34
“Total iron-binding capacity and transferrin saturation of serum samples were determined based on unsaturated iron-binding capacity (6, 24).”
BackgroundKasprowicz, K., Ziemann, E., Ratkowski, W., Laskowski, R., Kaczor, J. J., Dadci, R., & Antosiewicz, J. (2013) · PubMed · Cited by 34
Imatinib and spironolactone suppress hepcidin expression
Mleczko‐Sanecka, K., da Silva, A. R., Call, D., Neves, J. C., Schmeer, N., Damm, G., Seehofer, D., & Muckenthaler, M. U. (2017) · Haematologica · doi:10.3324/haematol.2016.162917 · Cited by 34
“(AI), caused by iron retention within body iron reservoirs and hypoferremia, develops due to hepcidin induction by immune activation.(7) The progression of the AI Disorders of iron metabolism are largely attributed to an excessive or insufficient expression of hepcidin, the master regulator of systemic iron homeostasi…”
Lee, J. H., Yang, D. H., Jang, S. Y., Choi, W. S., Kim, K. H., Lee, W. K., Bae, M. H., Park, H. S., Cho, Y., & Chae, S. C. (2013) · Clinical Cardiology · doi:10.1002/clc.22114 · Cited by 34
Sardo, U., Perrier, P., Cormier, K., Sotin, M., Personnaz, J., Medjbeur, T., Desquesnes, A., Cannizzo, L., Ruíz-Martínez, M., Thevenin, J., et al. (2024) · Blood · doi:10.1182/blood.2023022724 · Cited by 36
Self-citationThe SMAD Pathway Is Required for Hepcidin Response During Endoplasmic Reticulum Stress
Canali, S., Vecchi, C., Garuti, C., Montosi, G., Babitt, J. L., & Pietrangelo, A. (2016) · Endocrinology · doi:10.1210/en.2016-1258 · Cited by 33
Cavallaro, F., Duca, L., Pisani, L. F., Rigolini, R., Spina, L., Tontini, G. E., Munizio, N., Costa, E., Cappellini, M. D., Vecchi, M. L., et al. (2017) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/2017/6843976 · Cited by 33
“In healthy volunteers infused with IL-6, urinary excretion of hepcidin was increased several folds within two hours after infusion [28].”
BackgroundPrentice, A. M. (2017) · Annals of Nutrition and Metabolism · doi:10.1159/000480743 · Cited by 38
Serum Pro-hepcidin Could Reflect Disease Activity in Patients with Rheumatoid Arthritis
Kim, H., Kim, K., Yoon, S.-Y., Kim, S.-H., & Lee, S. (2010) · Journal of Korean Medical Science · doi:10.3346/jkms.2010.25.3.348 · Cited by 33
“Moreover, the hepcidin production is induced by a particular cytokine, IL-6, during inflammation (7).”
BackgroundInfluentialRed blood cell abnormalities and the pathogenesis of anemia in end‐stage renal disease
Georgatzakou, H. Τ., Antonelou, M. H., Papassideri, I. S., & Kriebardis, A. G. (2016) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201500127 · Cited by 33
“Finally, inflammatory cytokines affect iron metabolism and availability by regulating the expression of transferrin and lactoferrin receptors in erythroid cells and the expression of ferroportin—and thus hepcidin levels—in macrophages [47].”
BackgroundInflammation and diminished iron status: mechanisms and functional outcomes
Gaffney-Stomberg, E., & McClung, J. P. (2012) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e328357f63b · Cited by 33
Investigational therapies for renal disease-induced anemia
Schmid, H., & JELKMANN, W. E. B. (2016) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2016.1182981 · Cited by 33
“overload)[39]; hemojuvelin (HJV), a major co-receptor of BMP signaling; and IL-6 as the major inflammation-associated cytokine.[40] As a consequence, the BMP6/HJV/small mothers”
BackgroundComputational insight of dexamethasone against potential targets of SARS-CoV-2
Fadaka, A. O., Sibuyi, N. R. S., Madiehe, A. M., & Meyer, M. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1819880 · Cited by 33
“Additionally, based on the biological and the pathological roles of IL-6 in various diseases, it was anticipated that IL-6 targeting would constitute a novel treatment strategy for various immune-mediated diseases (Liuzzi et al., 2005; Nemeth et al., 2004; Nishimoto et al., 2005).”
BackgroundLiu, S., Dong, Z., Tang, W., Zhou, J. W., Guo, L., Gong, C., Liu, G., Wan, D., & Yin, Y. (2023) · Science China Life Sciences · doi:10.1007/s11427-022-2298-1 · Cited by 33
Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice
Pauk, M., Grgurević, L., Brkljačić, J. M., Kufner, V., Bordukalo-Nikšić, T., Grabušić, K., Razdorov, G., Rogić, D., Žuvić, M., Oppermann, H., et al. (2014) · International Orthopaedics · doi:10.1007/s00264-014-2550-4 · Cited by 33
“Hepcidin expression is induced by dietary [5] or parenteral [7] iron loading, suggesting its compensatory role in iron homeostasis.”
BackgroundNaz, N., Malik, I. A., Sheikh, N., Ahmad, S., Khan, S., Blaschke, M., Schultze, F. C., & Ramadori, G. P. (2012) · Laboratory Investigation · doi:10.1038/labinvest.2012.52 · Cited by 33
Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery
Hoppe, M., Lönnerdal, B. L., Hossain, B., Olsson, S., Nilsson, F. N., Lundberg, P., Rödjer, S., & Hulthén, L. (2008) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2007.11.008 · Cited by 33
“Since IL-6 has been proposed as a major inducer of hepcidin [11,12], via STAT3 (signal transducers and activators of transcription protein 3) [13], this work addressed questions regarding the impact of major surgery on prohepcidin, hepcidin, hematological iron markers and IL-6 in humans.”
BackgroundNew and old players in the hepcidin pathway
Camaschella, C., & Silvestri, L. (2008) · Haematologica · doi:10.3324/haematol.13724 · Cited by 33
“In humans, genetic inactivation of hepcidin causes a rare form of juvenile hemochromatosis,(6) whereas hepcidin overexpression in inflammation causes anemia of chronic diseases (ACD), which has features of iron restricted erythropoiesis.(7) The effect of hepcidin is clearly explained by its interaction with the cellul…”
BackgroundCurrent status of blood component therapy in surgical critical care
Napolitano, L. M. (2004) · Current Opinion in Critical Care · doi:10.1097/01.ccx.0000140948.98019.8a · Cited by 33
Bashandy, S. A. E., El‐Seidy, A. M. A., Ibrahim, F. A. A., Abdelrahman, S. S. M., Moussa, S. A. A., & Elbaset, M. A. (2023) · Scientific Reports · doi:10.1038/s41598-023-42550-y · Cited by 33
“The increase in the level of both IL6 and TNF-α was reported to enhance iron overload in tissues due to elevated hepcidin expression 70,71 .”
BackgroundNakagawa, H., Tamura, T., Mitsuda, Y., Goto, Y., Kamiya, Y., Kondo, T., Wakai, K., & Hamajima, N. (2014) · BMC Hematology · doi:10.1186/2052-1839-14-6 · Cited by 25
“induce hepcidin synthesis and corresponding hypoferremia during inflammation [11].”
BackgroundResultInfluentialThe actin-binding protein profilin 2 is a novel regulator of iron homeostasis
Luscieti, S., Galy, B., Gutiérrez, L., Reinke, M., Couso, J., Shvartsman, M., Pascale, A. D., Witke, W., Hentze, M. W., Boyl, P. P., et al. (2017) · Blood · doi:10.1182/blood-2016-11-754382 · Cited by 32
Intravenous iron therapy for non-anaemic, iron-deficient adults
Miles, L. F., Litton, E., Imberger, G. L., & Story, D. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013084.pub2 · Cited by 32
“Hepcidin impairs the function of the key iron regulatory protein, ferroportin, thereby preventing the transport of iron across basement membranes (Nemeth 2004a).”
BackgroundInfluentialToll-like receptors mediate induction of hepcidin in mice infected with Borrelia burgdorferi
Koening, C. L., Miller, J. C., Nelson, J. M., Ward, D. M., Kushner, J. P., Bockenstedt, L. K., Weis, J. J., Kaplan, J., & Domenico, I. D. (2009) · Blood · doi:10.1182/blood-2009-03-209577 · Cited by 32
Fertrin, K. Y., Lanaro, C., Franco‐Penteado, C. F., de Albuquerque, D. M., de Mello, M. R. B., Pallis, F. R., Bezerra, M. A. C., Hatzlhofer, B. L. D., Olbina, G., Saad, S. T. O., et al. (2013) · American Journal of Hematology · doi:10.1002/ajh.23649 · Cited by 32
“This may cause nontransferrin bound iron uptake by the reticuloendothelial system in SCD, sparing parenchymal tissue [7] and may increase hepcidin levels via interleukin-6 (IL-6) production, as found in anemia of inflammation [15].”
BackgroundNoguchi‐Sasaki, M., Sasaki, Y., Shimonaka, Y., Mori, K., & Fujimoto-Ouchi, K. (2016) · BMC Cancer · doi:10.1186/s12885-016-2305-2 · Cited by 32
“Because IL-6 is thought to be an important cause of the anemia of inflammation by inducing hepcidin expression [14], we used SAA levels as an indicator of IL-6 activity.”
Interleukin-10 Regulates Hepcidin in Plasmodium falciparum Malaria
Huang, H., Lamikanra, A., Alkaitis, M. S., Thézénas, M. L., Ramaprasad, A., Moussa, E., Roberts, D. J., & Casals‐Pascual, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088408 · Cited by 32
“Certainly, IL-6 has been associated with up-regulation of hepcidin and IL-6 levels are raised during acute infection [11].”
BackgroundThe effect of hepatitis B virus infection on hepcidin expression in hepatitis B patients.
Wang, X., Cheng, P., Jiang, F., & Jiao, X. (2013) · PubMed · Cited by 32
Ciniselli, C. M., Bortoli, M. D., Taverna, E., Varinelli, L., Pizzamiglio, S., Veneroni, S., Bonini, C., Orlandi, R., Verderio, P., & Bongarzone, I. (2015) · Expert Review of Proteomics · doi:10.1586/14789450.2015.1099436 · Cited by 32
“A direct relationship among IL6, hepcidin and iron has been shown in recent studies [4]; tumors and peritumoral tissues may express IL-6 via the Janus kinase 2-signal transducer and activator of transcription 3 pathway.”
BackgroundIron participated in breast cancer chemoresistance by reinforcing IL-6 paracrine loop
Li, J., He, K., Liu, P., & Xu, L. X. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.05.064 · Cited by 32
“It has been demonstrated that injection of IL-6 results in increased expression of hepcidin [29], which causes iron retention in macrophages.”
BackgroundMacDonell, S. O., Miller, J. C., Harper, M. J., Reid, M., Haszard, J. J., Gibson, R. S., & Houghton, L. A. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy052 · Cited by 32
Plasma Prohepcidin Positively Correlates with Hematocrit in Chronic Hemodialysis Patients
Hsu, S., Chiang, C., Chien, C., & Hung, K. (2006) · Blood Purification · doi:10.1159/000091453 · Cited by 32
“Experimental studies have demonstrated that interleukin-1 (IL-1), IL-6, and iron load induce expression of hepcidin [ ,”
BackgroundThe diagnostic and prognostic value of interleukin-6 in patients with soft tissue sarcomas
Hagi, T., Nakamura, T., Iino, T., Matsubara, T., Asanuma, K., Matsumine, A., & Sudo, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-08781-6 · Cited by 32
Immune cells dying from ferroptosis: mechanisms and therapeutic opportunities
Liu, J., Dong, R., Yuan, B., Xie, Y., Feng, Z., Zhou, S., Luan, F., & Chen, Y. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08204-9 · Cited by 32
Chen, Y., Xu, W., Yang, H. J., Shao, M., Xu, S., Deng, J., Gao, X., Liu, H., Shuai, Z., Xu, S., et al. (2020) · Immunological Investigations · doi:10.1080/08820139.2020.1742731 · Cited by 32
Nakao, K., Minato, N., & Üemoto, S. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0 · Cited by 34
Bauckman, K., Matsuda, R., Higgins, C. B., DeBosch, B. J., Wang, C., & Mysorekar, I. U. (2019) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00133.2018 · Cited by 31
Oral contraception does not alter typical post-exercise interleukin-6 and hepcidin levels in females
Sim, M., DAWSON, B. T., Landers, G. J., Swinkels, D. W., Tjalsma, H., Yeap, B. B., Trinder, D., & Peeling, P. (2013) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2013.11.008 · Cited by 31
Oncostatin M and leukemia inhibitory factor increase hepcidin expression in hepatoma cell lines
Kanda, J., Uchiyama, T., Tomosugi, N., Higuchi, M., Uchiyama, T., & Kawabata, H. (2009) · International Journal of Hematology · doi:10.1007/s12185-009-0443-x · Cited by 31
“Hepatic expression of hepcidin is also upregulated by inflammatory cytokines, including interleukin-6 (IL-6) [9, 12] and IL-1 [12, 13].”
BackgroundZhang, M., Liu, J., Guo, W., Liu, X., Liu, S., & Yin, H.-J. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2545 · Cited by 31
“Since IL-6 has been shown to increase hepcidin expression by activating the Stat3 signaling pathway (32,33), it was used in this study as a positive control to increase the p-Stat3 level (Fig.”
Ma, J., Li, R., Liu, Y., Qu, G., Liu, J. L., Guo, W., Song, H., Li, X., Liu, Y., Xia, T., et al. (2017) · Small · doi:10.1002/smll.201603830 · Cited by 31
Effect of marathon and ultra‐marathon on inflammation and iron homeostasis
Kaufmann, C. C., Wegberger, C., Tscharre, M., Haller, P. M., Piacková, E., Vujasin, I., Kassem, M., Tentzeris, I., Freynhofer, M. K., Jäger, B., et al. (2020) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.13869 · Cited by 31
Wang, C., Wang, X., Song, G., Xing, H., Yang, L., Han, K., & Chang, Y. (2020) · Journal of Food Biochemistry · doi:10.1111/jfbc.13578 · Cited by 31
COVID-19-associated-mucormycosis: possible role of free iron uptake and immunosuppression
Tabassum, T., Araf, Y., Moin, A. T., Rahaman, T. I., & Hosen, M. J. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06862-4 · Cited by 31
Fisiopatología del metabolismo del hierro: implicaciones diagnósticas y terapéuticas
Gómez, M. M., Garríguez, A. C., García‐Erce, J. A., & Ramirez, G. (2005) · Nefrología · Cited by 31
Timing of post-exercise carbohydrate ingestion: influence on IL-6 and hepcidin responses
Badenhorst, C. E., DAWSON, B. T., Cox, G. R., Laarakkers, C. M., Swinkels, D. W., & Peeling, P. (2015) · European Journal of Applied Physiology · doi:10.1007/s00421-015-3202-0 · Cited by 31
“…potential mechanism for altered iron metabolism within athletes (Roecker et al. 2005; Peeling et al. 2008; Latunde-Dada 2013), due to the hormone’s influence on the Fpn cellular iron export channels located on the basolateral intestinal enterocytes and macrophage cell surface (Nemeth et al. 2004b).”
BackgroundInfluentialBorges, Á. H., Weitz, J. I., Collins, G., Baker, J. V., Lévy, Y., Davey, R. T., Phillips, A. N., Neaton, J. D., Lundgren, J. D., & Deeks, S. G. (2014) · AIDS · doi:10.1097/qad.0000000000000344 · Cited by 31
Anderson, D. S., Heeney, M. M., Roth, U., Menzel, C., Fleming, M. D., & Steen, H. (2010) · Analytical Chemistry · doi:10.1021/ac902479p · Cited by 31
Antosiewicz, J., Kaczor, J. J., Kasprowicz, K., Laskowski, R., Kujach, S., Łuszczyk, M., Radzimiński, Ł., & Ziemann, E. (2013) · Cellular Immunology · doi:10.1016/j.cellimm.2013.06.006 · Cited by 31
Parajes, S., González‐Quintela, A., Franco, J. C., Quinteiro, C., Domínguez, F., & Loidi, L. (2010) · BMC Genetics · doi:10.1186/1471-2156-11-110 · Cited by 32
“Hepcidin is also upregulated in inflammation by interleukin 6 (IL-6) and other cytokines through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway [6,10,19].”
BackgroundHepcidin and GDF15 in anemia of multiple myeloma
Mei, S.-C., Wang, H., Fu, R., Qü, W., Xing, L., Wang, G., Song, J., Liu, H., Li, L., Wang, X., et al. (2014) · International Journal of Hematology · doi:10.1007/s12185-014-1626-7 · Cited by 31
“Studies in humans and animal models suggested that hepcidin overproduction is induced by inflammatory cytokines, such as IL-6, IL-1b, transforming growth factorb, and bone morphogenic proteins 2, 4, 6 and 9 [13–20].”
BackgroundGutschow, P., Schmidt, P. J., Han, H., Ostland, V., Bartnikas, T. B., Pettiglio, M. A., Herrera, C., Butler, J. S., Nemeth, E., Ganz, T., et al. (2014) · Haematologica · doi:10.3324/haematol.2014.116723 · Cited by 31
Self-citationMendoza, E., Duque, X., Franco, J. I. H., Maldonado, E. R., Morán, S., Martínez-Andrade, G. O., Salinas‐Rodríguez, A., & Martı́nez, H. (2019) · Nutrients · doi:10.3390/nu11092141 · Cited by 31
“It has been identified as the main regulator of iron absorption in the body [1,2].”
BackgroundVarghese, J., James, J. V., Anand, R., Narayanasamy, M., Rebekah, G. J., Ramakrishna, B., Nellickal, A. J., & Jacob, M. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108441 · Cited by 31
“Systemic inflammation has been shown to induce Hamp1 via interleukin-6 (IL-6) [28].”
BackgroundAntimicrobial Peptides in the Brain
Su, Y., Zhang, K., & Schluesener, H. J. (2010) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-010-0089-7 · Cited by 31
“…immunomodulatory, signaling molecule, regulator of iron homeostasis [Dringen et al. 2007; Hänninen et al. 2009; Jeyakumar et al. 2009; Nemeth et al. 2004; Wang et al. 2008; Zechel et al. 2006] AMPs antimicrobial peptides, CNS central nervous system, CRAMP cathelicidin-related…”
BackgroundCappelletti, M., Presicce, P., Ma, F., Senthamaraikannan, P., Miller, L. A., Pellegrini, M. A., Sim, M., Jobe, A. H., Divanovic, S., Way, S. S., et al. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001385 · Cited by 31
“Known as hypoferremia of inflammation, the cytokine-driven increase in hepcidin, largely mediated by IL6, decreases iron transport into plasma [56].”
BackgroundLiver-gut axis in the regulation of iron homeostasis
Darshan, D. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i35.4737 · Cited by 31
Red Blood Cell Distribution Width and Atrial Fibrillation
Wang, Z., Korantzopoulos, P. G., Roever, L., & Liu, T. (2020) · Biomarkers in Medicine · doi:10.2217/bmm-2020-0041 · Cited by 31
The role of tocilizumab in the management of rheumatoid arthritis
Ash, Z. R., & Emery, P. (2012) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2012.707178 · Cited by 30
Davis, M. R., Shawron, K., Rendina-Ruedy, E., Peterson, S., Lucas, E. A., Smith, B. J., & Clarke, S. L. (2011) · Journal of Nutrition · doi:10.3945/jn.111.144105 · Cited by 30
Hepcidin Attenuates Zinc Efflux in Caco-2 Cells
Hennigar, S. R., & McClung, J. P. (2016) · Journal of Nutrition · doi:10.3945/jn.116.237081 · Cited by 31
Koliaraki, V., Marinou, M., Samiotaki, M. K., Panayotou, G., Pantopoulos, K., & Mamalaki, A. (2008) · Biochimie · doi:10.1016/j.biochi.2008.01.012 · Cited by 30
Innate immunity of Florida cane toads: how dispersal has affected physiological responses to LPS
Gardner, S. T., Assis, V. R., Smith, K. M., Appel, A. G., & Mendonça, M. T. (2020) · Journal of Comparative Physiology B · doi:10.1007/s00360-020-01272-7 · Cited by 30
“1989), attracting neutrophils to sites of infection (Bickel 1993), and affecting oxygen transport (Nemeth et al. 2004), and metabolic rates (Tredget et al.”
BackgroundLangdon, J. M., Barkataki, S., Berger, A. E., Cheadle, C., Xue, Q., Sung, V., & Roy, C. N. (2014) · American Journal of Hematology · doi:10.1002/ajh.23856 · Cited by 30
“Its central role in driving the hypoferremia associated with anemia of inflammation [18] has made it a popular target for the development of drugs that might enhance erythropoiesis in various disease states [19–24].”
BackgroundHepcidin, an antimicrobial peptide is downregulated in ceruloplasmin-deficient mice
Guo, P., Cui, R., Chang, Y., Wu, W., Qian, Z., Yoshida, K., Qiao, Y.-T., Takeda, S., & Duan, X. (2008) · Peptides · doi:10.1016/j.peptides.2008.09.017 · Cited by 30
“[14] Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al.”
Metadata
- Authors
- Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Rigshospitalet (DK)
- Corresponding author
- Ganz, Tomas
- Venue
- Journal of Clinical Investigation
- Published
- 2004-05-01
- Volume
- 113
- Issue
- 9
- Pages
- 1271-1276
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC398432
- OpenAlex
- W2132155262
- Cited by
- 2,650
- References
- 40
- Citations by year
- 2026: 100 · 2025: 97 · 2024: 93 · 2023: 117 · 2022: 115 · 2021: 145 · 2020: 134 · 2019: 130 · 2018: 130 · 2017: 141 · 2016: 103 · 2015: 135 · 2014: 132 · 2013: 140 · 2012: 137
- FWCI
- 55.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- David Geffen School of Medicine, University of California, Los Angeles
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- interleukin-6, hepcidin, iron regulation, inflammation, cytokine signaling, liver, iron regulatory hormone
- MeSH terms
- Anemia, Animals, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Inflammation, Iron, Kupffer Cells, Mice, Inbred C57BL, Monocytes, RNA, Messenger, Interleukin-6, Mice, Knockout, Iron Metabolism Disorders, Reverse Transcriptase Polymerase Chain Reaction, Hepatocytes, Antimicrobial Cationic Peptides, Mice, Hepcidins
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