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)

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iron availability is transiently improved by intravenous iron medication in patients on chronic hemodialysis. 861 62

The host susceptibility to endotoxin (lipopolysaccharide, LPS), production of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) or phagocytosis in resident peritoneal macrophages were examined in iron-deficient and iron-loaded mice. Four groups of weanling male CD-1 mice were fed diet containing 7, 120, 5000 or 8000 ppm iron for 7 w. Body weight gain or hematocrit was not affected by iron consumption except for a lower weight gain in mice fed the 8000f1p4 iron diet. Iron-deficient and loaded diets produced a marked decrease and increase in liver iron concentration, respectively (P < 0.05). When challenged with an ip lethal dose of LPS, mortality was enhanced in iron-deficient and loaded mice (P = 0.035). The production of TNF-alpha and IL-1 alpha was assessed in the peritoneal macrophages stimulated by LPS in vitro. The production of IL-1 alpha and TNF-alpha was not altered in macrophages from iron-deficient mice. In contrast, macrophages from the 2 iron-loaded groups of mice produced more TNF-alpha (150% of control) without altering IL-1 alpha production. However, the total peritoneal leukocyte cell yield was not different among the treatment groups. Phagocytosis in the peritoneal macrophages determined by in vitro uptake of yeast cells was lower in the iron-deficient or loaded mice. This study indicates that iron deficiency and overload enhance LPS toxicity and impair phagocytosis, whereas excess iron also increases TNF-alpha production by macrophages.
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PMID:Effect of iron status on endotoxin-induced mortality, phagocytosis and interleukin-1 alpha and tumor necrosis factor-alpha production. 783 67

Mammary tumor incidence, natural killer (NK) cell activity, and tumor necrosis factor-alpha (TNF-alpha) activity were measured in iron (Fe)-deficient and iron-replete rats treated with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Female weanling rats were fed AIN-76 diets: the iron-deficient group was fed 5 mg Fe/kg diet; the control group was fed 50 mg Fe/kg diet; the food-restricted group was fed 50 mg Fe/kg diet in the amount consumed by the iron-deficient group; and the replete group was fed 5 mg Fe/kg diet for 45 days and then 50 mg Fe/kg diet. After six weeks of feeding, the rats were given a single intragastric dose of DMBA. Feeding the iron-deficient diet for 20 weeks reduced hematocrit, hemoglobin, liver iron, and tumor iron values and increased spleen weight. Dietary iron repletion for 14 weeks reversed these effects of iron deficiency. Splenic NK cell cytotoxicity against YAC-1 cells was highest in the control group. Repleting rats with 50 mg Fe/kg diet corrected iron deficiency but did not restore NK cell cytotoxicity. No significant differences in macrophage TNF-alpha bioactivity were found among groups. Cumulative tumor incidence over all weeks was lowest in the iron-deficient rats. Iron repletion during the promotion phase of tumorigenesis attenuates the protective effects of iron deficiency. Food restriction to the extent present in the iron-deficient group did not protect against tumorigenesis. The iron-deficient group had the lowest tumor burden and delayed onset of tumors. Iron deficiency significantly reduces tumor incidence in DMBA-treated rats by mechanisms other than NK cell cytotoxicity, TNF-alpha activity, and food restriction.
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PMID:Iron repletion attenuates the protective effects of iron deficiency in DMBA-induced mammary tumors in rats. 858 49

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

Although anemia is a common finding among human immunodeficiency (HIV)-infected infants in sub-Saharan Africa, the factors contributing to the pathogenesis of anemia have not been well characterized. We sought to characterize the relative contribution of iron deficiency and chronic disease to the anemia among infants. Hemoglobin, ferritin, erythropoietin, tumor necrosis factor-alpha (TNF-alpha), neopterin, CD4(+) lymphocyte count and plasma HIV load were measured in 165 HIV-infected and 39 uninfected 9-mo-old infants seen in an outpatient pediatric clinic in Kampala, Uganda. Among HIV-infected and uninfected infants, the prevalence of anemia (hemoglobin < 110 g/L) was 90.9 and 76.9%, respectively (P = 0.015), and the prevalence of iron deficiency anemia (hemoglobin < 110 g/L and ferritin < 12 microg/L) was 44.3 and 45.4%, respectively (P = 0.92). The relatively higher prevalence of anemia among HIV-infected infants was attributed to the anemia of chronic disease. Among infants with and without iron deficiency, the fitted regression line was log(10) plasma erythropoietin = 2.86 - 0.016.hemoglobin, and log(10) plasma erythropoietin = 4.11 - 0.028.hemoglobin, respectively, with a difference in the slope of the regression lines between log(10) erythropoietin and hemoglobin among infants with and without iron deficiency (P = 0.049). Infants in Uganda have an extremely high prevalence of anemia, and nearly half of the anemia is due to iron deficiency. The erythropoietin response to anemia appears to be upregulated among infants with iron deficiency.
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PMID:Iron deficiency anemia is highly prevalent among human immunodeficiency virus-infected and uninfected infants in Uganda. 1188 May 66

Resistance to recombinant human erythropoietin occurs in a small but important proportion of hemodialysis patients. This may be due to increased immune activation because pro-inflammatory cytokines inhibit erythropoiesis in vitro. Using FACScan flow cytometry, the proportion of PMA/ionomycin-stimulated T cells expressing cytokines ex vivo was compared in 18 poor responders to erythropoietin, 14 good responders to erythropoietin, and 14 normal controls. CD4(+) T cells from poor responders expressed more interferon-gamma (IFN-gamma; 19 +/- 6%) compared with good responders (11 +/- 6%, P < 0.001) and controls (12 +/- 6%, P < 0.01). Similarly, CD4+ T cells from poor responders expressed more tumor necrosis factor-alpha (TNF-alpha; poor responders: 51 +/- 19% versus good responders: 27 +/- 15% [P < 0.01] and controls: 30 +/- 19% [P < 0.01]). CD4+ expression of IL-10 was also enhanced (poor responders: 1.6 +/- 1.1% versus good responders: 0.7 +/- 0.6% [P < 0.05] and controls: 0.5 +/- 0.2% [P < 0.01]). Likewise, CD4+ expression of interleukin-13 (IL-13) was increased (poor responders: 4.4 +/- 4.2% versus good responders: 1.6 +/- 1.7% [P < 0.05] and controls: 1.6 +/- 1.5% [P < 0.05]). CD8+ T cells from poor responders also showed enhanced expression of cytokines. For IFN-gamma, poor responder expression was 48 +/- 20% compared with 31 +/- 17% (P < 0.05) for good responders and 23 +/- 15% (P < 0.01) for controls. TNF-alpha expression for poor responders was 41 +/- 21% versus 25 +/- 14% for good responders (P < 0.05) and 21 +/- 15% for controls (P < 0.01). IL-10 expression for poor responders was 2.0 +/- 1.2% (good responders: 0.7 +/- 0.6% [P < 0.01]; controls: 0.5 +/- 0.2% [P < 0.001]). These data indicate that T cells from poor responders are in an enhanced activation state possibly as a result of chronic inflammation. In the absence of any other cause (such as iron deficiency), the overproduction of cytokines may account for hyporesponsiveness to erythropoietic therapy in patients with renal failure.
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PMID:Increased expression of erythropoiesis inhibiting cytokines (IFN-gamma, TNF-alpha, IL-10, and IL-13) by T cells in patients exhibiting a poor response to erythropoietin therapy. 1281 37

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

Plasma levels of tumor necrosis factor-alpha (TNF-alpha) are significantly raised in malaria infection and TNF-alpha is thought to inhibit intestinal iron absorption and macrophage iron release. This study investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of kappa light polypeptide gene enhancer in B cells (lkappaBL), inhibitor-like 1 and lymphotoxin alpha (LTA), in relation to nutritional iron status and anemia, in a cohort of 780 children across a malaria season. The prevalence of iron deficiency anemia (IDA) increased over the malaria season (P < .001). The TNF(-308) AA genotype was associated with an increased risk of iron deficiency (adjusted OR 8.1; P = .001) and IDA (adjusted OR 5.1; P = .01) at the end of the malaria season. No genotypes were associated with IDA before the malaria season. Thus, TNF appears to be a risk factor for iron deficiency and IDA in children in a malaria-endemic environment and this is likely to be due to a TNF-alpha-induced block in iron absorption.
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PMID:Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia in West African children. 1898 75

Hepcidin is a hormone that regulates the intestinal absorption of iron and its release from the reticuloendothelium. The objective of this study was to determine the use of hepcidin for kidney disease patients with a diagnosis of iron deficiency pretransplantation by evaluating the soluble transferrin receptor (sRTfR-F) index as a marker for iron deficiency. This transverse study of 164 pretransplant patients determined hematometry and conventional markers related to iron metabolism, as well as soluble transferrin receptor (sTfR), its index (sTfR-F), and serum hepcidin concentrations. The following markers of inflammation (MIF) were also assessed C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and soluble TNF-alpha receptor (s-TNF-alphaR). Among the studied patients, 11.4% showed an absolute iron deficiency with ferritin concentrations < 100 ng/mL, a mean hepcidin value of 120.7 +/- 38.5 ng/mL, and a mean sTfR-F value of 1.03 +/- 0.3; 18.2% of patients displayed a ferritin > 800 ng/mL with mean hepcidin and sTfR-F values of 147.5 +/- 36.6 ng/mL and 0.54 +/- 0.2, respectively. Iron deficiency was not observed in the other patients when considering the conventional markers: ferritin > 100 ng/mL and transferrin saturation (ST) > 20%. However, this study showed that determination of hepcidin concentrations together with M/F improved the identification of iron deficiency in pretransplant patients by 21.6%.
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PMID:Hepcidin and iron deficiency in pre-kidney transplant patients. 1971 36


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