Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant erythropoietin (r-EPO) was administered to 37 patients with advanced, transfusion-dependent and chemo-resistant multiple myeloma (MM), at the fixed dose of 10,000/U s.c., 3 times a week, for 2 months. Thirteen patients (35.1%) achieved a significant response in terms of complete abolition of red cell transfusions. Factors significantly predictive of response were: a) inappropriate production of endogenous EPO, as expressed by a reduced observed/predicted ratio; b) presence of a consistent number of circulating erythroid precursors BFU-E; c) low serum levels of tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with inhibitory activity on erythropoiesis; d) a single line of previously received chemotherapy. Renal failure, bone marrow plasma cell infiltration, serum levels of IL-6 and other main clinical and laboratory parameters did not affect significantly the response to r-EPO. High fluorescence reticulocytes (HFR) and soluble transferrin receptor (sTfR) values were useful to detect an early stimulation of erythropoiesis in responders, while a high percentage of circulating hypochromic erythrocytes (HE), as assessed by an automated counter, identified those patients developing functional iron deficiency during r-EPO treatment. We conclude that about one-third of severely anemic patients with advanced MM, unresponsive to chemotherapy, may benefit by r-EPO therapy. The clinical management of these patients can be accomplished using non-invasive parameters, such as sTfR, HFR and HE.
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PMID:Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory multiple myeloma: role of cytokines and monitoring of erythropoiesis. 922 86

Dietary copper (Cu) deficiency impairs both innate and acquired branches of immunity. Specific roles of Cu in the activation and effector activities of host-defense cells remain largely unknown. The effects of Cu status on effector activities of a monocytic cell line were investigated as an initial step in the elucidation of specific functions of Cu in phagocytic cells. Exposure of differentiating U937 human promonocytic cells to 5 micromol/L 2,3, 2-tetraamine (tet), a high affinity Cu chelator, for 4 d decreased cellular Cu by 62% without altering cellular Cu,Zn-superoxide dismutase (SOD) activity, Zn content, mitochondrial activity and protein synthesis. In contrast, Cu deficiency suppressed the respiratory burst activity and markedly compromised the ability of U937 cells to kill Salmonella. Similarly, treatment of RAW264.7 murine macrophages with 5 micromol/L tet decreased cell Cu by 78% and Cu,Zn-SOD activity by 15% and increased bacterial survival by 180%. The tet-induced impairment of respiratory burst and bactericidal activities was blocked in cultures supplemented with Cu, but not Zn or Fe. In addition, lipopolysaccharide (LPS)-induced secretion of the inflammatory mediators, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and prostaglandin E(2) (PGE(2)), was decreased by 30-60% in tet-treated U937 cells. Flow cytometric analysis of the surface antigens CD11b and CD71 showed that the suppressed activities of Cu-deficient cells were not due to an attenuation in the degree of differentiation or secondary iron deficiency. These data demonstrate that U937 cells provide a useful model for examining the biochemical roles of Cu in monocyte activity.
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PMID:Copper deficiency suppresses effector activities of differentiated U937 cells. 1082 6

Worldwide, over 40% of children have iron deficiency anaemia, frequently associated with infections. Certain cytokines are involved in both immune activation/response to infection and iron transport/metabolism. We therefore assessed the relations among iron deficiency, cytokine production and lymphocyte activation markers in 142 hospitalized Malawian children. We examined peripheral blood lymphocyte antigens/cytokine production using four- colour flow cytometry and serum transferrin receptor (TfR) levels, an inverse measure of iron status unaffected by acute illness or infection, with an enzyme-linked immunosorbent assay. Wilcoxon rank sum tests and logistic regression analyses (LRA) were performed. Iron deficiency (TfR > or = 10 microg/ml) versus TfR < 10 microg/ml, was associated with higher percentages of lymphocytes producing: (a) induced or spontaneous IL-6 (medians: induced, 15.9% for iron-deficient children versus 8.8% for iron-replete children, P = 0.002; spontaneous, 24.4% versus 13.0%, P < 0.001) and (b) induced IFN-gamma (medians:18.4% versus 12.4%, P = 0.006). The percentages of CD8(+) T cells spontaneously producing IL-6 and of all lymphocytes producing induced TNF-alpha and IFN-gamma in the same cell had the strongest relationships to iron deficiency (b = + 0.0211, P = 0.005 and b = + 0.1158, P = 0.012, respectively, LRA) and were also positively related to the co-expression of the T cell activation markers HLA DR and CD38. Severe iron deficiency (TfR > or = 30 microg/ml) was associated with the percentage of lymphocytes producing induced IL-4 (medians: 0.5% versus 1.6%, P < 0.010). The cytokine patterns associated with iron deficiency in our study would preserve iron stores but also preferentially retain the activation capabilities of T cells, albeit not necessarily other immune cells, until a critical level of iron depletion is reached.
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PMID:The effects of iron deficiency on lymphocyte cytokine production and activation: preservation of hepatic iron but not at all cost. 1173 64

The anaemia associated with chronic renal failure is multi-factorial. Although a relative erythropoietin deficiency is a major factor, it has also been recognized in recent times that uraemia is a chronic inflammatory state, and thus patients with renal failure also develop anaemia due to mechanisms associated with chronic inflammation. Thus, patients with chronic renal failure have activation of various immune cells, both monocytes and T-cells. These mononuclear cells have also been shown to release pro-inflammatory cytokines such as IL-1, IL-6, TNF-alfa and interferon gamma. These cytokines, particularly TNF-alfa and interferon gamma, are known to cause significant suppression of erythropoiesis. The exact molecular mechanism for this effect is not yet clear, but interferon gamma is an important stimulator of apoptosis in various cell types, including erythroid progenitor cells. This effect may be potentiated by other cytokines such as TNF-alfa, and this might then antagonise the anti-apoptotic action of erythropoietin on erythroid progenitors cells, thus reducing responsiveness to exogenous erythropoietic therapy. Chronic renal failure is also associated with increased hepcidin production which may also exacerbate the anaemia by inducing a functional iron deficiency in such patients.
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PMID:Hyporesponsiveness to erythropoietic therapy due to chronic inflammation. 1628 56

TNF-alpha is a pleitropic cytokine that expresses both pro- and anti-inflammatory activity and transgenic mice expressing human tumor necrosis factor-alpha (TNF-alpha) exhibit a progressive polyarthritis that models rheumatoid arthritis (RA). One of the common comorbidities of RA is anemia of chronic disease (ACD). The purpose of these experiments was to study the changes in the bone marrow and peripheral blood that accompany polyarthritis in TNF-alpha transgenic mice in an effort to better understand the pathogenesis of myelodysplasia and ACD. Polychromatic cytometry, hematology and serum cytokine analysis were used to study the pathogenesis of ACD in human TNF-alpha transgenic mice. Our hematological evaluation revealed a mild, compensated, microcytic hypochromic anemia, and monocytosis. In the bone marrow, we observed alterations in cell kinetics, decreased relative expression of transferrin receptor and increased apoptosis and cell death in several late precursor cell populations. Although significant levels of human TNF-alpha were found in the serum, neither change in serum murine erythropoietin nor any significant difference observed in serum levels of murine IL-beta, IL-5, IL-6, IL-10, IL-12(p70), IL-17, TNF-alpha, IFNgamma, GM-CSF, MIP-1alphaJE, MCP-5 was observed. Tg197 mice develop a compensated, microcytic, hypochromic anemia, and a functional iron deficiency by 9 weeks of age. Changes in peripheral blood are reflected in alterations in cell kinetics, transferrin receptor expression and markedly increased apoptosis and cell death in the bone marrow indicating that TNF-alpha may contribute to myelodysplasia in ACD. Moreover, since human TNF-alpha can interact only with murine TNFR1, our data suggest that TNFR1 may play an important role in the development of ACD.
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PMID:Myelodysplasia and anemia of chronic disease in human tumor necrosis factor-alpha transgenic mice. 1820 95

Recently discovered peptide hormone hepcidin is the key regulator of systemic iron homeostasis. Iron metabolism is regulated in response to variations in hepcidin plasma levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. The early studies showed that hypoxia, iron concentration, and inflammation influence hepcidin levels, but the exact mechanism remained elusive. Very recently, different research groups discovered that IL-6, through the Jak/STAT-3 signaling pathway, is involved in regulation of hepcidin levels in response to inflammatory stimuli. In this review we present a general view of hepcidin biology, with emphasis on regulation in inflammatory conditions.
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PMID:IL-6 - STAT-3 - hepcidin: linking inflammation to the iron metabolism. 1833 66

Iron deficiency (ID) and iron deficiency anemia (IDA) are the most common iron disorders throughout the world. ID and IDA, particularly caused by increased iron requirements during pregnancy, represent a high risk for preterm delivery, fetal growth retardation, low birth weight, and inferior neonatal health. Oral administration of ferrous sulfate to cure ID and IDA in pregnancy often fails to increase hematological parameters, causes adverse effects and increases inflammation. Recently, we have demonstrated safety and efficacy of oral administration of 30% iron saturated bovine lactoferrin (bLf) in pregnant women suffering from ID and IDA. Oral administration of bLf significantly increases the number of red blood cells, hemoglobin, total serum iron and serum ferritin already after 30 days of the treatment. The increasing of hematological values by bLf is related to the decrease of serum IL-6 and the increase of serum hepcidin, detected as prohepcidin, whereas ferrous sulfate increases IL-6 and fails to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA in pregnant women.
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PMID:Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant women. 2040 5

Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.
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PMID:Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. 2049 29

Anemia is a common clinical problem in end-stage renal disease (ESRD). Despite adequate erythropoiesis-stimulating agent (ESA) supplementation, some ESRD patients still have suboptimal hemoglobin levels, and iron deficiency and inflammation are recognized as the two most common causes. Hepcidin, a newly discovered key regulator of iron homeostasis, is found to be accumulated in ESRD. As it controls iron uptake and release, better reflecting real-time iron demand and availability, hepcidin might become a target in the management of iron deficiency and ESA resistance in dialysis patients. For their pleiotropic functions apart from lipid-modulation, statins are also used as anti-inflammatory or immune-modulating agents. In this study, we applied simvastatin for the purpose of influencing serum prohepcidin level in a group of maintenance hemodialysis patients. Thirty-three ESRD patients undergoing hemodialysis were enrolled and assigned to experimental and hemodialysis control groups according to their lipid profile. Nineteen healthy adults were chosen as a normal control group. The subjects in the experimental group took 20 mg simvastatin orally per night for eight weeks, and those in the hemodialysis control group took no statins or any other lipid-modulating drugs. Before and after the experiment, the serum prohepcidin concentrations, plasma IL-6, and serum C-reactive protein (CRP), ferritin, hemoglobin, albumin, total cholesterol, glycerinate, and LDL and HDL cholesterol levels were determined. Of the 33 hemodialysis patients, the serum prohepcidin concentration was (175.8 +/- 52.9) ng/mL, significantly higher than that in the normal control group (149.5 +/- 24.2) ng/mL (P = 0.048). In the experimental group, the serum prohepcidin level was (156.7 +/- 51.9) ng/mL before treatment, and (190.6 +/- 49.6) ng/mL after eight weeks (P = 0.127). In the hemodialysis control group, the serum prohepcidin level was (190.6 +/- 49.6) ng/mL at the beginning, and (193.5 +/- 36.0) ng/mL after eight weeks (P = 0.728). In the experimental group, after taking simvastatin for eight weeks the serum total cholesterol and triglyceride levels had lowered by 18.6% (P = 0.004) and 55.1% (P = 0.007), respectively. The plasma IL-6, serum CRP, ferritin, hemoglobin, albumin, and LDL and HDL cholesterol levels in both the hemodialysis group remained unchanged. According to our preliminary study, eight weeks of 20 mg simvastatin did not significantly change the serum prohepcidin, high-sensitive CRP, or IL-6 concentrations in the group of maintenance hemodialysis patients.
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PMID:How does short-term low-dose simvastatin influence serum prohepcidin levels in patients with end-stage renal disease? A pilot study. 2060 84

Iron homeostasis in pregnancy compensates for increased iron requirements and in women of child-bearing age for iron loss in menses. Oral administration of ferrous sulfate, prescribed to cure iron deficiency (ID) and ID anemia (IDA), often fails to increase hematological parameters and causes adverse effects. Recently, we demonstrated safety and efficacy of bovine lactoferrin (bLf) in pregnant women suffering from ID/IDA. Two clinical trials were conducted on pregnant and non-pregnant women of child-bearing age suffering from ID/IDA. In both trials, women received oral administration of bLf 100 mg/twice/day (Arm A), or ferrous sulfate 520 mg/day (Arm B). Hematological parameters, serum IL-6 and prohepcidin were assayed before and after therapy. Unlike ferrous sulfate, bLf increased hematological parameters (P less than 0.0001). In pregnant women, bLf decreased serum IL-6 (P less than 0.0001), and increased prohepcidin (P=0.0007). In non-pregnant women bLf did not change the low IL-6 levels while it increased prohepcidin (P less than 0.0001). Ferrous sulfate increased IL-6 (P less than 0.0001) and decreased prohepcidin (P=0.093). bLf established iron homeostasis by modulating serum IL-6 and prohepcidin synthesis, whereas ferrous sulfate increased IL-6 and failed to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA.
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PMID:Lactoferrin efficacy versus ferrous sulfate in curing iron disorders in pregnant and non-pregnant women. 2064 53


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