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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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
“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.
- Checkable: passes — It can be checked against evidence.
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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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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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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.
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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.
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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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
“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
“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
“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
“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
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Ferroptosis in Neurological Disease
David, S., Ryan, F., Jhelum, P., & Kroner, A. (2022) · The Neuroscientist · doi:10.1177/10738584221100183 · Cited by 43
Hurrell, B. P., Sakano, Y., Shen, S. M.-C., Helou, D. G., Li, M., Shafiei-Jahani, P., Kazemi, M. H., Sakano, K., Li, X., Quach, C., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adk4728 · Cited by 42
Hepcidin Concentrations in Serum and Urine Correlate with Iron Homeostasis in Preterm Infants
Müller, K., Springer, L., Poets, C. F., Westerman, M. E., & Franz, A. R. (2012) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2011.12.030 · Cited by 41
Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload
Preziosi, M., Singh, S., Valore, E. V., Jung, G., Popovic, B., Poddar, M., Nagarajan, S., Ganz, T., & Monga, S. P. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.03.012 · Cited by 41
Self-citationRegulating ferroportin‐1 and transferrin receptor‐1 expression: A novel function of hydrogen sulfide
Zhang, M., Yang, G., Zhou, Y., Qian, C., Mu, M., Ke, Y., & Qian, Z. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27431 · Cited by 41
“…consistent with findings reported by other researchers in mice (Deschemin & Vaulont, 2013; Rivkin et al., 2016) and in human volunteers (Kemna, Pickkers, Nemeth, van der Hoeven, & Swinkels, 2005; Nemeth et al., 2004), providing further evidence that LPS can induce anemia of inflammation in mice.”
ResultAdamson, J. W. (2009) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2008.12.009 · Cited by 42
Iron delocalisation in the pathogenesis of malarial anaemia
Nweneka, C. V., Doherty, C. P., Cox, S. E., & Prentice, A. M. (2009) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/j.trstmh.2009.08.007 · Cited by 43
Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort
Atkinson, M. A., Kim, J. Y., Roy, C. N., Warady, B. A., White, C. T., & Furth, S. L. (2014) · Pediatric Nephrology · doi:10.1007/s00467-014-2991-4 · Cited by 41
“Among the four main regulators of hepcidin production (hypoxia, erythropoiesis, inflammation, and iron status), inflammation may be a relatively more significant promoter in patients with underlying glomerular disease compared with those with congenital forms of CKD, although the specific mechanisms for this remain to…”
BackgroundSkarpańska-Stejnborn, A., Basta, P., Sadowska, J., & Pilaczyńska-Szczȩśniak, Ł. (2014) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-014-0048-5 · Cited by 41
Layoun, A., Huang, H., Calvé, A., & Santos, M. M. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.01.046 · Cited by 43
Diagnosis and treatment of anemia in patients with inflammatory bowel disease
Mücke, V. T. (2016) · Annals of Gastroenterology · doi:10.20524/aog.2016.0083 · Cited by 43
“It reduces iron absorption in cases of iron overload or upon induction by proinflammatory cytokines, including interleukin (IL) -6 and bone morphogenetic protein [25,26].”
BackgroundBalance of cardiac and systemic hepcidin and its role in heart physiology and pathology
Vela, D. (2017) · Laboratory Investigation · doi:10.1038/labinvest.2017.111 · Cited by 41
Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases
Petzer, V., Theurl, I., & Weiß, G. (2018) · Pharmaceuticals · doi:10.3390/ph11040135 · Cited by 41
“From a systemic point of view, hepcidin, a liver-derived hormone, has been found to be the master regulator of iron homeostasis, controlling cellular iron efflux [2].”
BackgroundSemba, R. D., Ricks, M. O., Ferrucci, L., Xue, Q., Chaves, P. H. M., Fried, L. P., & Guralnik, J. M. (2007) · Aging Clinical and Experimental Research · doi:10.1007/bf03324699 · Cited by 42
The effect of psychological stress on iron absorption in rats
Chen, J., Shen, H., Chen, C., Wang, W., Yu, S., Zhao, M., & Li, M. (2009) · BMC Gastroenterology · doi:10.1186/1471-230x-9-83 · Cited by 41
“And interleukin-6 (IL-6) can stimulate hepcidin expression in vivo and in vivo [ 18 ,19].”
BackgroundJacolot, S., Férec, C., & Mura, C. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2008.01.006 · Cited by 42
Hepcidin is a Potential Regulator of Iron Status in Chronic Kidney Disease
Tsuchiya, K., & Nitta, K. (2012) · Therapeutic Apheresis and Dialysis · doi:10.1111/1744-9987.12001 · Cited by 42
“Regulation by hypoxia Decreased hepcidin expression has been reported in response to hypoxia in vivo (28,29), and the decrease in expression may be attributable to the effect of hypoxia on erythropoietin (EPO) expression and erythropoietic activity via a direct interaction with hepatocyte EPO receptors (30).”
Backgroundde Montalembert, M., Ferster, A., Colombatti, R., Rees, D. C., Gulbis, B., & on behalf of the European Network for Rare and Congenital Anaemias (2010) · American Journal of Hematology · doi:10.1002/ajh.21865 · Cited by 41
Hepcidin in anemia of chronic heart failure
Divakaran, V. G., Mehta, S., Yao, D., Hassan, S. A., Simpson, S., Wiegerinck, E. T. G., Swinkels, D. W., Mann, D. L., & Afshar‐Kharghan, V. (2010) · American Journal of Hematology · doi:10.1002/ajh.21902 · Cited by 41
Iron Supplementation Therapy, A Friend and Foe of Mycobacterial Infections?
Agoro, R., & Mura, C. (2019) · Pharmaceuticals · doi:10.3390/ph12020075 · Cited by 41
“In mice, upon inflammation, high hepcidin levels decrease intestinal iron absorption and the release of recycled iron from macrophages, inducing hyposideremia of acute inflammation that are associated with low plasma iron and transferrin saturation [100,107].”
BackgroundKartikasari, A. E. R., Wagener, F. A. D. T. G., Yachie, A., Wiegerinck, E. T. G., Kemna, E., & Winkels, D. W. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00494.x · Cited by 41
“This acts on the one hand as a crucial causative factor in pathogenesis of anaemia of inflammation, by retention of heme-derived iron in the iron storage sites, thereby withholding it from the erythroid compartment [7–9] On the other hand, hepcidin suppression is observed in anemias, necessary to increase iron supply…”
BackgroundRegulation of hepcidin in HepG2 and RINm5F cells
Fein, E., Merle, U., Ehehalt, R., Herrmann, T. R. W., & Kulaksiz, H. (2007) · Peptides · doi:10.1016/j.peptides.2007.01.016 · Cited by 41
Treatment of anemia in difficult-to-manage patients with chronic kidney disease
Raichoudhury, R., & Spinowitz, B. (2021) · Kidney International Supplements · doi:10.1016/j.kisu.2020.12.006 · Cited by 41
“deficiency may be caused by increased hepcidin production,(9,11) which is stimulated by proinflammatory cytokines.(12,13) Elevated hepcidin levels promote sequestration of”
BackgroundThe role of ferroptosis in the development of acute and chronic kidney diseases
Zhou, Y., Zhang, J., Guan, Q., Tao, X., Wang, J., & Li, W. (2022) · Journal of Cellular Physiology · doi:10.1002/jcp.30901 · Cited by 41
Doyle, M. K., Rahman, M. U., Frederick, B., Birbara, C. A., de Vries, D., Toedter, G., Wu, X., Chen, D., Ranganath, V. K., Westerman, M. E., et al. (2013) · Rheumatology · doi:10.1093/rheumatology/kes381 · Cited by 40
Salama, S. A., Al-Harbi, M. S., Abdel‐Bakky, M. S., & Omar, H. A. (2015) · Biochimie · doi:10.1016/j.biochi.2015.06.006 · Cited by 40
Pradeep, A. R., Anuj, S., & Arjun Raju, P. (2010) · Journal of Periodontology · doi:10.1902/jop.2010.100336 · Cited by 42
Anemia of Inflammation in Critically Ill Patients
Sihler, K. C., & Napolitano, L. M. (2008) · Journal of Intensive Care Medicine · doi:10.1177/0885066608320836 · Cited by 40
“Likewise anti-IL-6 antibodies completely reversed hepatocyte hepcidin induction by lipopolysaccharide (LPS).(10) Further proof comes from the demonstration that IL-6 infusion into human subjects rapidly increased hepcidin concentrations.”
BackgroundInfluentialPhysiopathologie de la maladie de Still de l'adulte
Arlet, J. B., Huong, D. U. L. T., Pouchot, J., & Pietté, J. C. (2004) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2004.11.021 · Cited by 40
Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies
Sheikh, N., Batusic, D. S., Dudás, J., Tron, K., Neubauer, K., Saile, B., & Ramadori, G. P. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00586.2005 · Cited by 40
“(34), that is to say that IL-6 may be sufficient to induce hepcidin gene expression in acute inflammation.”
BackgroundFunctional role of endothelial transferrin receptor 1 in iron sensing and homeostasis
Fisher, A. L., Wang, C., Xu, Y., Joachim, K., Xiao, X., Phillips, S., Moschetta, G. A., Alfaro-Magallanes, V. M., & Babitt, J. L. (2022) · American Journal of Hematology · doi:10.1002/ajh.26716 · Cited by 42
Activated macrophages induce hepcidin expression in HuH7 hepatoma cells
Matak, P., Chaston, T. B., Chung, B., Srai, S. K., McKie, A. T., & Sharp, P. (2009) · Haematologica · doi:10.3324/haematol.2008.003400 · Cited by 40
Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation
Baringer, S. L., Simpson, I. A., & Connor, J. R. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15819 · Cited by 41
Langdon, J. M., Yates, S. C., Femnou, L. K., McCranor, B. J., Cheadle, C., Xue, Q., Vaulont, S., Civin, C. I., Walston, J. D., & Roy, C. N. (2014) · American Journal of Hematology · doi:10.1002/ajh.23670 · Cited by 40
“We expect the high iron content of the diet prevented the detection of a significant increase in Hepc mRNA in WT mice, as a prior report has indicated [5].”
BackgroundResultInfluentialWagner, M., Ashby, D. R., Kurtz, C. B., Alam, A., Busbridge, M., Raff, U., Zimmermann, J., Heuschmann, P. U., Wanner, C., & Schramm, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123072 · Cited by 42
Yang, J., Liu, C., Li, L., Tu, X., & Lu, Z. (2019) · Canadian Respiratory Journal · doi:10.1155/2019/3853454 · Cited by 40
“Other inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, (IL)-8, and IL-1β, affect iron metabolism and bone marrow function; this situation inhibits erythropoiesis and the entry of larger juvenile cells into the peripheral circulation, thereby increasing the RDW [28, 29].”
BackgroundFisher, A. L., Sangkhae, V., Presicce, P., Chougnet, C. A., Jobe, A. H., Kallapur, S. G., Tabbah, S., Buhimschi, C. S., Buhimschi, I. A., Ganz, T., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.135321 · Cited by 40
“Known as hypoferremia of inflammation, the cytokine-driven increase in hepcidin (13) decreases iron transport into plasma, so that NTBI is not available”
BackgroundSelf-citationUpregulation of hepcidin by interleukin-1β in human hepatoma cell lines
Inamura, J., Ikuta, K., Jimbo, J., SHINDO, M., SATO, K., Torimoto, Y., & KOHGO, Y. (2005) · Hepatology Research · doi:10.1016/j.hepres.2005.08.005 · Cited by 40
Hemodialysis Central Venous Catheters as a Source of Inflammation and Its Implications
Hung, A. M., & Ikizler, T. A. (2008) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2008.00444.x · Cited by 40
“Data indicate that hepcidin-mediated hypoferremia occurs shortly after interleukin-6 production increases (41,43,44).”
BackgroundIron overload and its impact on outcome of patients with hematological diseases
Franke, G., Kubasch, A. S., Cross, M. A., Vučinić, V., & Platzbecker, U. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100868 · Cited by 40
Azab, S. F. A., & Esh, A. M. H. (2013) · Annals of Hematology · doi:10.1007/s00277-013-1813-2 · Cited by 40
Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women
Angeli, A., Lainé, F., Lavenu, A., Ropert, M., Lacut, K., Gissot, V., Sacher-Huvelin, S., Jezequel, C., Moignet, A., Laviolle, B., et al. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9875-4 · Cited by 40
“Conversely, hepcidin concentrations increase when iron stores are high (12,13) and in the presence of inflammation (14,15), which decreases intestinal absorption and iron release from storage.”
BackgroundJohnson, D. W., Pascoe, E. M., Badve, S. V., Dalziel, K., Cass, A., Clarke, P., Ferrari, P., McDonald, S. P., Morrish, A. T., Pedagogos, E., et al. (2014) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2014.06.020 · Cited by 39
“CRP (mg/L) 10 [3-32] 13 [3-23] Table 1 (Cont’d).”
Advancements in anemias related to chronic conditions
Guidi, G. C., & Santonastaso, C. L. (2010) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2010.264 · Cited by 39
Nuhu, F., Seymour, A. L., & Bhandari, S. (2019) · Antioxidants · doi:10.3390/antiox8100498 · Cited by 39
“Studies have shown the elevation of inflammatory markers and concomitant upregulated expression of hepcidin [46,47] can lead to functional iron deficiency (ID) anaemia in CKD [48,49].”
BackgroundRosa, L., Cutone, A., Conte, M. P., Campione, E., Bianchi, L., & Valenti, P. (2022) · BioMetals · doi:10.1007/s10534-022-00427-z · Cited by 39
“Differently from Fpn, hepcidin is up-regulated by several factors as iron stores and IL-6, IL-1α and IL-1β (Nemeth et al.”
BackgroundInfluentialCampostrini, N., Castagna, A., Zaninotto, F., Bedogna, V., Tessitore, N., Poli, A., Martinelli, N., Lupo, A., Olivieri, O., & Girelli, D. (2010) · BioMed Research International · doi:10.1155/2010/329646 · Cited by 39
“For example, hepcidin may increase because of reduced glomerular filtration, iron therapy, and inflammation, with interleukin-6 as a well-known stimulus for its production [13, 15].”
Lutz, S. Z., Hennige, A. M., Feil, S. C., Peter, A., Gerling, A., Machann, J., Kröber, S. M., Rath, M., Schürmann, A., Weigert, C., et al. (2011) · Diabetes · doi:10.2337/db10-0760 · Cited by 41
“Macrophage-derived IL-6 may also cause anemia via induction of the iron-regulatory hormone hepcidin in hepatocytes (51).”
Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance
Lee, S. W., Kim, J., Lim, H. J., Hwang, Y., Kim, S. W., Chung, W., Oh, K., Ahn, C., Lee, K., & Sung, S. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-04664-y · Cited by 39
Gonciarz, R. L., & Renslo, A. R. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.01.015 · Cited by 39
Costa, E. M., Pereira, B. J. G., Rocha‐Pereira, P., Rocha, S., Reis, F., Castro, E. M. B., Teixeira, F. J., Miranda, V. M. P., Faria, M., Loureiro, A., et al. (2008) · American Journal of Nephrology · doi:10.1159/000121478 · Cited by 39
“Furthermore, in vitro stimulation of fresh human hepatocytes by proinflammatory IL-6 showed strong induction of hepcidin mRNA, indicating that this cytokine may be the mediator of hepcidin induction in inflammation [ , ,”
BackgroundManco, M., Alisi, A., Real, J.-M. F., Equitani, F., Vito, R. D., Valenti, L. V. C., & Nobili, V. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.12.007 · Cited by 39
“Indeed, IL6 is responsible for hypoferraemia in chronic inflammation by inducing the hepatic synthesis of hepcidin [14].”
BackgroundHuang, C., Chang, C., Kuo, C., Huang, C., Chiu, T.-W., Lin, C., & Liu, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104495 · Cited by 39
“sufficient for the induction of hepcidin during inflammation, and that the IL-6–hepcidin axis was responsible for inflammationinduced hypoferremia [37].”
BackgroundG-CSF Drives a Posttraumatic Immune Program That Protects the Host from Infection
Gardner, J. C., Noel, J. G., Nikolaidis, N. M., Karns, R. A., Aronow, B. J., Ogle, C. K., & McCormack, F. X. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302752 · Cited by 39
Mayeur, C., Kolodziej, S. A., Wang, A., Xu, X., Lee, A., Yu, P. B., Shen, J., Bloch, K. D., & Bloch, D. B. (2015) · Haematologica · doi:10.3324/haematol.2014.111484 · Cited by 38
“achieved after oral administration were sufficient to increase hemoglobin levels in AI, mice were challenged with turpentine, a well-established animal model of AI, which induces hepatic hepcidin gene expression in an IL6dependent manner.(13) Mice were injected with turpentine weekly for three weeks,(9,14) and were tr…”
MethodHyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications
Regenboog, M., Kuilenburg, A. B. P., Verheij, J., Swinkels, D. W., & Hollak, C. E. M. (2016) · Blood Reviews · doi:10.1016/j.blre.2016.05.003 · Cited by 41
“For example, interleukin-6 is a regulator of hepcidin synthesis in the liver [58] and this pro-inflammatory cytokine can be increased in GD [56].”
BackgroundColafrancesco, S., Scrivo, R., Barbati, C., Conti, F., & Priori, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01439 · Cited by 38
“Although tocilizumab dramatically reduced CRP levels, of the four critically ill patients who received one single dose of the drug, three died, and the remaining one worsened.”
BackgroundInfluentialAnaemia in chronic obstructive pulmonary disease. Does it really matter?
Portillo, K., Martínez‐Rivera, C., & Manzano, J. R. (2013) · International Journal of Clinical Practice · doi:10.1111/ijcp.12125 · Cited by 38
Causes and consequences of inflammation on anemia management in hemodialysis patients
Chawla, L. S., & Krishnan, M. (2009) · Hemodialysis International · doi:10.1111/j.1542-4758.2009.00352.x · Cited by 38
Role of hepcidin and iron metabolism in the onset of prostate cancer
Zhao, B., Li, R., Cheng, G., Li, Z., Zhang, Z., Li, J., Zhang, G., Bi, C., Chen, H., Yang, L., et al. (2018) · Oncology Letters · doi:10.3892/ol.2018.8544 · Cited by 38
“Hepcidin is a hormone-regulating molecule that is synthesized and secreted by liver cells and serves a vital role in maintaining the in vivo iron metabolic balance (10,11).”
Fisher, A. L., & Babitt, J. L. (2021) · Developmental Dynamics · doi:10.1002/dvdy.372 · Cited by 41
Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
Cardoneanu, A., Burlui, A., Macovei, L. A., Bratoiu, I., Richter, P., & Rezuş, E. (2022) · Biomedicines · doi:10.3390/biomedicines10020318 · Cited by 39
“Due to the stimulatory effect of hepcidin formation, the iron transporter is blocked in the gut (ferroportin 1) [34].”
BackgroundErdemir, E. O., Nalçacı, R., & Çağlayan, O. (2008) · European Journal of Dentistry · doi:10.1055/s-0039-1697363 · Cited by 38
Strategic Targets of Essential Host-Pathogen Interactions
Blasi, F., Tarsia, P., & Aliberti, S. (2005) · Respiration · doi:10.1159/000083394 · Cited by 39
“Hepcidin gene expression in the liver increases significantly within hours of infection with Gram-positive or Gram-negative pathogens, and infusion of IL-6 in human healthy volunteers [”
BackgroundImmunotherapeutic Implication of IL-6 Blockade
Tanaka, T., & Kishimoto, T. (2011) · Immunotherapy · doi:10.2217/imt.11.147 · Cited by 39
Green tea activity and iron overload induced molecular fibrogenesis of rat liver
Albasher, G. I. (2017) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2017.08.007 · Cited by 38
The Mechanisms of Anaemia in Trypanosomosis: A Review
Mbaya, A. W., Kumshe, H., & Nwosu, C. O. (2012) · InTech eBooks · doi:10.5772/29530 · Cited by 38
“However, in more recent studies (Nemeth et al., 2004) suggested that anaemia in trypanosomosis involving hypofferaemia was caused by IL-6 and hepeidin.”
ResultPre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients
Szkandera, J., Gerger, A., Liegl‐Atzwanger, B., Stotz, M., Samonigg, H., Ploner, F., Stojaković, T., Leithner, A., & Pichler, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107297 · Cited by 38
“On the other hand, some cytokines, such as interleukin-6 (IL-6), have been demonstrated to induce anemia [25,26].”
BackgroundAshenafi, S., Bekele, A., Aseffa, G., Amogne, W., Kassa, E., Aderaye, G., Worku, A., Bergman, P., & Brighenti, S. (2022) · Nutrients · doi:10.3390/nu14163318 · Cited by 33
“This includes IL-6, which can stimulate hepatic expression of the acutephase protein hepcidin, known to block iron uptake in the intestine and to reduce iron release by macrophages [6,30].”
BackgroundHepcidin and Iron Metabolism in Experimental Liver Injury
Bloomer, S. A., & Brown, K. E. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.04.005 · Cited by 38
Nutritional status of Tajik children and women: Transition towards a double burden of malnutrition
Jaeggi, T., Zandberg, L., Bahruddinov, M., Kiefer, S., Rahmarulloev, S., & Wyss, K. (2019) · Maternal and Child Nutrition · doi:10.1111/mcn.12886 · Cited by 38
“Inflammation has been shown to decrease ferroportin, through increased production of hepcidin, and therefore reduce iron absorption, as well as the release of storage iron (Nemeth et al., 2004).”
BackgroundEffects of Iron Status on Adaptive Immunity and Vaccine Efficacy: A Review
Stoffel, N. U., & Drakesmith, H. (2024) · Advances in Nutrition · doi:10.1016/j.advnut.2024.100238 · Cited by 39
“It's expression is triggered by in fl ammation, primarily through the cytokine IL-6 [73].”
BackgroundReid, B. M., & Georgieff, M. (2023) · Nutrients · doi:10.3390/nu15173798 · Cited by 38
Thanapholsart, J., Khan, E., Ismail, T. F., & Lee, G. (2022) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2022.08.016 · Cited by 39
Bustinduy, A. L., & King, C. H. (2013) · Elsevier eBooks · doi:10.1016/b978-0-7020-5101-2.00053-4 · Cited by 38
Boutou, A. K., Pitsiou, G. G., Stanopoulos, I., Kontakiotis, T., Kyriazis, G., & Argyropoulou, P. (2012) · QJM · doi:10.1093/qjmed/hcs024 · Cited by 37
Valerio, L. G. (2007) · Toxicology Mechanisms and Methods · doi:10.1080/15376510701556690 · Cited by 38
“The net effect is that Trf without bound iron (apotransferrin) and the TrfR recycle themselves 503 Mammalian Iron Metabolism by returning to the cell surface and dissociating to participate in another cycle of cellular iron uptake (Andrews 2000b).”
BackgroundInfluentialAdvances in cell death mechanisms involved in viral myocarditis
Yang, Y., Li, W., You, B., & Zhou, C. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.968752 · Cited by 37
“VMC caused by SARS-CoV2 can cause a cytokine storm, especially IL-6, and alter systemic iron metabolism (93, 94).”
BackgroundMeroño, O., Cladellas, M., Recasens, L., García‐García, C., Ribas, N., Bazán, V., Farré, N., Sainz, Á., Colet, J. C., & Bruguera, J. (2012) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2012.03.008 · Cited by 37
“A more pronounced inflammatory state could explain the occurrence of nosocomial anemia, since in some patients with ACS there would be an increase in circulating cytokines that would suppress erythropoiesis, thereby blocking iron stores and inhibiting intestinal absorption.(32) One hypothesis is that in some patients,…”
BackgroundTransforming Growth Factor β1 (TGF-β1) Activates Hepcidin mRNA Expression in Hepatocytes
Chen, S., Feng, T., Spasić, M. V., Altamura, S., Breitkopf‐Heinlein, K., Altenöder, J., Weiß, T. S., Dooley, S., & Muckenthaler, M. U. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.691543 · Cited by 37
Hepcidin as a new biomarker for detecting autologous blood transfusion
Leuenberger, N., Barras, L., Nicoli, R., Robinson, N., Baume, N., Lion, N., Barelli, S., Tissot, J., & Saugy, M. (2016) · American Journal of Hematology · doi:10.1002/ajh.24313 · Cited by 37
“inflammation [34]; therefore, WBC, CRP, and IL-6 levels in each”
BackgroundDisordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes
Ivy, K. S., & Ferrell, P. B. (2018) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-018-0463-9 · Cited by 37
Hepcidin in Trauma: Linking Injury, Inflammation, and Anemia
Sihler, K. C., Raghavendran, K., Westerman, M. E., Ye, W., & Napolitano, L. M. (2010) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e3181f066d5 · Cited by 37
Hepcidin in anemia of chronic kidney disease: review for the pediatric nephrologist
Atkinson, M. A., & White, C. T. (2011) · Pediatric Nephrology · doi:10.1007/s00467-011-1832-y · Cited by 37
“When infused into healthy volunteers, IL-6 causes an abrupt decrease in serum iron levels and increase in urinary hepcidin concentration within hours [35].”
BackgroundImpaired expression of duodenal iron transporters in Dahl salt-sensitive heart failure rats
Naito, Y., Tsujino, T., Fujimori, Y., Sawada, H., Akahori, H., Hirotani, S., Ohyanagi, M., & Masuyama, T. (2010) · Journal of Hypertension · doi:10.1097/hjh.0b013e3283434784 · Cited by 38
Fürst, D. E., Kay, J., Wasko, M. C., Keystone, E. C., Kavanaugh, A., Deodhar, A. A., Murphy, F. T., Magnus, J. H., Hsia, E. C., Hsu, B. L., et al. (2013) · Rheumatology · doi:10.1093/rheumatology/ket233 · Cited by 37
Imamiya, R., Shinohara, A., Yakura, D., Yamaguchi, T., Ueda, K., Oguro, A., Minamiyama, Y., Ichikawa, H., Horiguchi, Y., & Osada‐Oka, M. (2023) · mBio · doi:10.1128/mbio.03051-22 · Cited by 38
“the concentration of iron in extracellular fluid and plasma decreases dramatically (32, 33).”
BackgroundHepcidin contributes to Swedish mutant APP-induced osteoclastogenesis and trabecular bone loss
Guo, H.-H., Xiong, L., Pan, J., Lee, D., Liu, K., Ren, X., Wang, B., Yang, X., Cui, S., Mei, L., et al. (2021) · Bone Research · doi:10.1038/s41413-021-00146-0 · Cited by 37
Blood Iron Homeostasis: Newly Discovered Proteins and Iron Imbalance
Bleackley, M. R., Wong, A. Y. K., Hudson, D. M., Wu, C., & MacGillivray, R. T. A. (2009) · Transfusion Medicine Reviews · doi:10.1016/j.tmrv.2008.12.001 · Cited by 38
Shanmugam, N. K. N., Ellenbogen, S., Trebicka, E., Wang, L., Mukhopadhyay, S., Lacy‐Hulbert, A., Gallini, C. A., Garrett, W. S., & Cherayil, B. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038136 · Cited by 37
“Although TNFa has been shown previously to inhibit hepcidin expression in a hepatocyte cell line [15], the results shown here represent, to the best of our knowledge, the first demonstration that this cytokine has a negative regulatory effect on hepcidin in clinically relevant in vivo models of inflammation.”
ResultLi, W., Zhou, X., Xu, S., Cao, N., Li, B., Chen, W., Yang, B., Yuan, M., & Xu, D. (2022) · Poultry Science · doi:10.1016/j.psj.2022.101725 · Cited by 37
Alfieri, D. F., Lehmann, M. F., Flauzino, T., de Araújo, M. C. M., Pivoto, N., Tirolla, R. M., Simão, A. N. C., Maes, M. H. J., & Reiche, E. M. V. (2020) · Neurotoxicity Research · doi:10.1007/s12640-020-00221-0 · Cited by 36
“…stress can modulate ferritin expression, with IL-6 inducing the production of hepcidin, the main regulator of plasma iron levels; the IL-6–hepcidin axis may be responsible for the hypoferremia and increased expression of ferritin upregulating an inflammatory microenvironment (Nemeth et al. 2004).”
BackgroundBajbouj, K., Shafarin, J., Allam, H., Madkour, M. I., Awadallah, S. M., El-Serafi, A. T., Sandeep, D., & Hamad, M. A. (2018) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0043-124077 · Cited by 36
Systematic review of anaemia and inflammatory markers in chronic obstructive pulmonary disease
Hoepers, A. T. D. C., Pizzichini, M. M. M., & Fröde, T. S. (2015) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12357 · Cited by 36
“2).(45,47) The increase or decrease in the hepcidin level is controversial in COPD.”
BackgroundHuang, T., Gu, W., Wang, B., Zhang, Y., Cui, L., Yao, Z., Zhao, C., & Xu, G. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.01.020 · Cited by 36
Hepcidin and ferritin levels in restless legs syndrome: a case–control study
Chenini, S., Delaby, C., Rassu, A.-L., Barateau, L., Vialaret, J., Hirtz, C., Dupuy, A., Lehmann, S., Jaussent, I., & Dauvilliers, Y. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-68851-0 · Cited by 36
“…hepcidin levels have also been reported in other conditions (e.g., hemochromatosis 30 , metabolic syndrome 31 , atherosclerosis 32,33 , inflammation 34,35 , renal and cardiovascular diseases 36–38 ) that may be associated with RLS, but almost not in our current RLS population due to our exclusion…”
BackgroundMethodInfluentialBandach, I., Segev, Y., & Landau, D. (2021) · Scientific Reports · doi:10.1038/s41598-021-85778-2 · Cited by 37
Iron deficiency and biomarkers of inflammation: a 3-year prospective analysis of the DO-HEALTH trial
Wieczorek, M., Schwarz, F., Sadlon, A., Abderhalden, L. A., Molino, C. D. G. R. C., Spahn, D. R., Schaer, D. J., Orav, E. J., Egli, A., & Bischoff-Ferrari, H. A. (2021) · Aging Clinical and Experimental Research · doi:10.1007/s40520-021-01955-3 · Cited by 36
Improvement in hemoglobin levels in patients with ankylosing spondylitis treated with infliximab
Braun, J., van der Heijde, D. M. F. M., Doyle, M. K., Han, C., Deodhar, A. A., Inman, R. D., de Vlam, K., Burmester, G. R., den Bosch, F. E. V., Xu, S., et al. (2009) · Arthritis Care & Research · doi:10.1002/art.24865 · Cited by 36
Sim, M., DAWSON, B. T., Landers, G. J., Trinder, D., & Peeling, P. (2014) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2013-0067 · Cited by 36
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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