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<p>Four studies that analyzed hepcidin as a potential biomarker and/or the correlation between hepcidin and ferritin.</p

Delta Hgb is higher in anemic patients who received IV iron.

<p>Delta Hgb values represent the difference of the hemoglobin value that was measured directly prior to surgery and the baseline hemoglobin level. <b>(A)</b> Baseline Hgb values were higher in non-anemic patients (14.3g/dl [13.48, 14.9], n = 48) than in both anemic patients with (10.8g/dl [10.05, 11.7], n = 79, *p<0.0001) and without (11.3g/dl [10.1, 11.93], n = 64, ^#p<0.0001) IV iron treatment. <b>(B)</b> Delta Hgb values were higher in anemic patients who were administered with IV iron (n = 40) (0.45g/dl [0.05, 1.05] vs. 0.1g/dl [-0.48, 0.73], *p = 0.03) compared to anemic patients without IV iron treatment (n = 26). <b>(C)</b> Patients with an increase in Hgb levels of ≥0.6g/dl were considered responders. Delta Hgb values were higher in the group of responders (1.1g/dl [0.8, 1.45], n = 19 patients) compared to the delta Hgb values in the group of anemic non-responders (0.1g/dl [-0.3, 0.3], n = 21 patients).</p

Correlation of serum hepcidin levels with parameters of the iron status.

<p>Serum hepcidin levels of the three patient groups of non-anemic controls, anemic patients treated with IV iron and anemic patients without IV iron treatment, were correlated to the iron parameters. The x- and y-scales are depicted logarithmic (log10). Values of “0” were replaced with 0.01 in order to depict them in the logarithmic graph. Serum hepcidin levels correlated with <b>(A)</b> serum iron levels (n = 146 XY-pairs (n = 9 non-anemics, n = 58 anemics without IV iron, n = 79 anemics plus IV iron); r = 0.19; Spearman *p = 0,02), <b>(B)</b> transferrin protein levels (n = 143 XY-pairs (n = 6 non-anemics, n = 58 anemics without IV iron, n = 79 anemics plus IV iron); r = -0,55; Spearman *p<0.0001), <b>(C)</b> ferritin levels (n = 143 XY-pairs (n = 6 non-anemics, n = 58 anemics without IV iron, n = 79 anemics plus IV iron); r = 0,75 Spearman *p<0.0001) and <b>(D)</b> transferrin saturation (n = 142 XY-pairs (n = 5 non-anemics, n = 58 anemics without IV iron, n = 79 anemics plus IV iron); r = 0.37; Spearman *p<0.0001).</p

Multivariable regression analysis of delta Hgb.

<p>Multivariable regression analysis of delta Hgb.</p

Characteristics of responders and non-responders.

<p>Characteristics of responders and non-responders.</p

Multivariable regression analysis for potential confounding effects.

<p>Multivariable regression analysis for potential confounding effects.</p

Comparison of hepcidin levels in the groups of responders and non-responders.

<p>Serum hepcidin levels were lower in anemic patients with a good response to IV iron (2.07ng/ml [0.25, 7.97], n = 19) compared to anemic patients with an impaired response (10.62ng/ml [3.93, 34.77], n = 21; *p = 0.04).</p

Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation

<div><p>Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA), but controversial in anemia of inflammation (AI). Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed <i>Brucella abortus</i> (BA) model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet) prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.</p></div

Hepatic mRNA levels of pSTAT3, MCP-1, SOD2 and activin B in the liver of WT mice after BA and intravenous iron injection.

<p><b>(A)</b> Phosphorylated STAT3 levels compared to α-tubulin in the liver of C57BL/6 mice 4h after intraperitoneal BA or PBS administration followed by intravenous iron or PBS treatment for an additional 2h. <b>(B)</b> Hepatic MCP-1 mRNA levels were determined in WT mice after intraperitoneal BA or PBS administration followed by intravenous iron or PBS injection for an additional 2h (n = 3, 2-way ANOVA P<0,0001; **P = 0.007: PBS/PBS vs BA/PBS; *P = 0.02: PBS/PBS vs BA/iron; **P = 0.007: PBS/iron vs BA/PBS); (*P = 0.02: PBS/iron vs BA/iron; **P = 0.008: BA/PBS vs BA/iron; not shown in the graph). <b>(C)</b> Hepatic SOD2 mRNA levels in WT mice 4h after intraperitoneal BA or PBS administration followed by intravenous iron or PBS treatment for an additional 2h (n = 3, 2-way ANOVA P = 0.0002; **P = 0.004: PBS/PBS vs BA/PBS; **P = 0.004: PBS/PBS vs BA/iron); (**P = 0.006: PBS/iron vs BA/PBS; **P = 0.007: PBS/iron vs BA/iron, not shown in graph). <b>(D)</b> Hepatic activin B mRNA levels in WT mice 4h after intraperitoneal BA or PBS administration followed by intravenous iron or PBS injection for an additional 2h (n = 3, 2-way ANOVA P<0,0001; **P = 0.009: PBS/PBS vs BA/PBS; ***P = 0.0002: PBS/PBS vs BA/iron); (**P = 0.009: PBS/iron vs BA/PBS; ***P = 0.0003: PBS/iron vs BA/iron, not shown in graph).</p

Hepcidin response to iron treatment depends on the diets.

<p>WT mice were challenged with or without intraperitoneal BA injection and 14d later treated with or without intravenous iron. <b>(A)</b> Hepatic hepcidin mRNA levels 24h after iron treatment in mice fed a regular iron diet (black bars) or an iron deficient diet (white bars) (iron deficient diet: n = 4, 2-way ANOVA P = 0.006; *P = 0.01: PBS/PBS vs BA/iron; ***P = 0.0002: BA/PBS vs BA/iron). <b>(B)</b> Hepcidin mRNA levels 7d after the iron treatment in mice as in (A) (iron deficient diet: n = 4, 2-way ANOVA P = 0.0007; *p = 0.02: PBS/PBS vs BA/PBS; **P = 0.001: BA/PBS vs BA/iron). <b>(C)</b> Liver iron content (LIC) was determined in C57BL/6 mice fed a regular or iron deficient diet. LIC 14d after BA and 24h after intravenous iron administration are shown (regular diet: n = 3–4, 2-way ANOVA P = 0.002; **P = 0.008: PBS/PBS vs BA/PBS, iron deficient diet: n = 4, 2-way ANOVA, P < 0.0001; **P = 0.005: PBS/PBS vs BA/iron; **P = 0.004: BA/PBS vs BA/iron). <b>(D)</b> LIC 14d after BA and 7d after iron treatment in mice fed a regular or an iron deficient diet (iron deficient diet: n = 4, 2-way ANOVA P = 0.0002; *P = 0.01: PBS/PBS vs BA/iron; *P = 0.01: BA/PBS vs BA/iron).</p