Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron balance in human beings is maintained by the control of absorption. Recent observations have demonstrated that a peptide hormone, hepcidin, is the principal regulator of iron homeostasis. It is produced in the liver in response to increasing iron stores. It is also induced by interleukin-6 (IL-6) in infectious and inflammatory diseases. Hepcidin restricts both iron absorption and iron release from stores. Disorders that affect the duodenum or stomach directly, particularly gluten enteropathy and H. pylori infections, also impair iron absorption by damaging enterocytes or reducing gastric acid output. Hepcidin secretion is suppressed by accelerated erythropoiesis even when iron stores are increased. This appears to account for the contribution that excessive absorption makes to the iron overload seen in patients with iron-loading anemias such as thalassemia major. There is some evidence suggesting that two nutritional deficiency disorders (deficiencies of vitamin A and riboflavin) lead to impaired iron absorption or utilization, but further research is needed to reconcile conflicting experimental observations.
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PMID:Influence of infection/inflammation, thalassemia and nutritional status on iron absorption. 1821 23

Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis (HD) patients, one of the main causes of death is cardiovascular disease. In animals, trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B(12) deficiency-induced HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B(12), trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP), and interleukin-6 concentrations were determined in 122 hemodialysis patients. When patients were divided into groups according to their tHcy, we found no significant differences in concentrations of cobalt, copper, and total protein, while nickel was higher, and folate, vitamin B(12), and iron were lower in patients with lower than higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations of folate (r = -0.302, p < 0.006), vitamin B(12) (r = -0.347, p < 0.0001), nickel (r = -0.289, p < 0.006), and CRP (r = -0.230, p < 0.02) and positively with serum albumin (r = 0.316, p < 0.0004) and hemoglobin (r = 0.329, p < 0.0001) values. No relationship between tHcy and serum concentrations of cobalt, copper, iron, or other laboratory parameters was found in HD patients. The effect of cobalt and nickel on homocysteine production was assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine production in human PBMCs. These results suggest that nickel might also be involved in the regulation of the methionine-folate cycle in humans, as was demonstrated in animal experiments.
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PMID:Relationship between serum nickel and homocysteine concentration in hemodialysis patients. 1846 90

Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.
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PMID:Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery. 1849 62

Anemia is a widespread public health problem. The psychological stress decreases serum iron level and inhibits erythropoiesis. However, the molecular mechanisms involved, leading to iron mal-regulation are not well known. We used a communication box paradigm to induce psychological stress and found that serum iron level decreased after 3d while liver iron storage increased after 7d. Moreover, psychological stress up-regulated expressions of interleukin-6 (IL-6) and hepcidin, while down-regulating ferroportin expression after 3d. These changes were blocked by the injection of IL-6 monoclonal antibody. In conclusion, the IL-6-hepcidin axis is up-regulated by psychological stress in rats, resulting in hypoferremia and increase of hepatic iron storage.
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PMID:Psychological stress induces hypoferremia through the IL-6-hepcidin axis in rats. 1854 Nov 41

Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD.
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PMID:Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway? 1854 42

The relationship between serum hepcidin, a key regulator of body iron homeostasis, and erythropoiesis was investigated before and after stem cell transplantation in 31 patients with hematopoietic malignancies. Serum hepcidin-25 was monitored using a liquid chromatography-tandem mass spectrometry-based assay system. Other iron- and erythropoiesis-related parameters and known hepcidin regulators, such as interleukin-6 and growth differentiation factor-15, were also monitored. The serum hepcidin level peaked one week after stem cell transplantation, followed by a gradual decrease with a parallel change in interleukin-6 and a reciprocal change in reticulocyte count. Multivariate regression analysis demonstrated that the serum hepcidin level at four weeks after stem cell transplantation showed significant inverse correlations with erythropoietic activity markers, such as the soluble transferrin receptor, but not with growth differentiation factor-15. These results indicate the existence of an unknown functional erythropoiesis-associated circulating factor, other than growth differentiation factor-15, that negatively regulates hepcidin production in stem cell transplantation settings.
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PMID:Serum hepcidin level and erythropoietic activity after hematopoietic stem cell transplantation. 1864 Oct 32

In many important human pathogens, such as Shigella and Salmonella spp., the bacterial type III secretion (T3S) apparatus is required to initiate inflammation via activation of caspase-1- or NF-kappaB-dependent genes. Using an ex vivo infection model, the goal of the present study was to determine whether the chlamydial T3S apparatus also modulates the host inflammatory response. Infections of mouse peritoneal macrophages were performed with Chlamydia muridarum, and the expression of inflammatory cytokines was monitored by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Since there is no current genetic system for Chlamydia spp., blockade of T3S was accomplished pharmacologically using a T3S inhibitor called INP0007. It has been previously shown that INP0007 also blocks chlamydial growth in vitro and that the addition of exogenous iron completely reverses this deficit. The addition of iron to INP0007-treated C. muridarum-infected macrophages not only restored chlamydial growth deficit caused by INP0007 but also led to a multi-inclusion phenotype. Overall, T3S inhibition led to decreased interleukin-6 (IL-6), IL-1beta, and CXCL10, whereas the tumor necrosis factor alpha levels were unchanged. Rescue of chlamydial growth by addition of iron sulfate did not restore cytokine production, implying that the decreased expression of many cytokines during infection was dependent on T3S and not solely on growth. In addition, the observation that the greatest effects of INP0007 were seen at late time points during infection suggests that a temporally regulated T3S effector protein(s) may be triggering the host cytokine response.
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PMID:Role for the chlamydial type III secretion apparatus in host cytokine expression. 1885 36

Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflammatory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9+/-10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48% fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance.
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PMID:Plasma prohepcidin as a negative acute phase reactant after large cardiac surgery with a deep hypothermic circulatory arrest. 1909 40

Serum transferrin, estimated by total iron-binding capacity (TIBC), may be a marker of protein-energy wasting (PEW) in maintenance hemodialysis (MHD) patients. We hypothesized that low TIBC or its fall over time is associated with poor clinical outcomes. In 807 MHD patients in a prospective 5-year cohort, associations of TIBC and its changes over time with outcomes were examined after adjustment for case-mix and markers of iron stores and malnutrition-inflammation including serum interleukin-6, iron and ferritin. Patients with serum TIBC >or=250 mg/dl had higher body mass index, triceps and biceps skinfolds and mid-arm muscle circumference and higher serum levels of iron but lower ferritin and inflammatory markers. Some SF-36 quality of life (QoL) components were worse in the lowest and/or highest TIBC groups. Mortality was incrementally higher in lower TIBC levels (p-trend <0.001). Adjusted death hazard ratio was 1.75 (95% CI: 1.00-3.05, p = 0.05) for TIBC <150 compared to TIBC of 200-250 mg/dl. A fall in TIBC >20 mg/dl over 6 months was associated with a death hazard ratio of 1.57 (95% CI: 1.04-2.36, p = 0.03) compared to the stable TIBC group. Hence, low baseline serum TIBC is associated with iron deficiency, PEW, inflammation, poor QoL and mortality, and its decline over time is independently associated with increased death risk.
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PMID:Association of serum total iron-binding capacity and its changes over time with nutritional and clinical outcomes in hemodialysis patients. 1913 18

Anti-anaemic drug ferric-sorbitol citrate showed immunomodulatory effects, activating NF-kappaB in peritoneal macrophages, which consequently secrete tumour necrosis factor-alpha (TNF-alpha). TNF-alpha activates NF-kappaB in spleen cells. The aim of this study was to investigate the effect of iron polyisomaltosate, an iron (Fe(3+)) compound, on serum iron, interleukin-6 (IL-6) and serotonin (5-HT) concentration, neutrophil activity, and NF-kappaB activation in peritoneal macrophages and spleen cells in rats. Female Wistar rats were injected i.p. with 7.5mg iron/kg of iron polyisomaltosate 1.5, 3, 6, 24 and 48h before sacrifice. Serum iron, 5-HT and IL-6 concentration was determined by colorimetric, spectrofluorimetric and ELISA methods, neutrophil activity by a chemiluminescence assay, and NF-kappaB expression/activation by a Dot-Blot method. Iron polyisomaltosate significantly increased serum iron and 5-HT concentrations during the first 6h, IL-6 levels 3 and 6h, and diminished respiratory burst of granulocytes 1.5h after the injection. Iron polyisomaltosate stimulated activation of p65, p50 and RelB subunits of NF-kappaB in the peritoneal macrophages after 6h, and RelB subunit was additionally increased after 24 and 48h. In the spleen cells iron polyisomaltosate stimulated p65 subunit after 48h and RelB subunit after 24h. The results showed time-dependent immunomodulatory effects of iron polyisomaltosate. These effects might be achieved via induction of the intracellular signalling for NF-kappaB activation in peritoneal macrophages and later in spleen cells, together with increase of serum 5-HT, and IL-6 but with diminished respiratory burst of granulocytes. Iron polyisomaltosate presumably activated reactive oxygen species resulting in the stimulation of the acute phase reactants in the liver.
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PMID:Acute immunomodulatory effects of iron polyisomaltosate in rats. 1916 90


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