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)

A redox-sensitive nuclear factor, NF-kappa B, induces transcription of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in macrophages. The present study has investigated the role of iron in NF-kappa B activation and TNF-alpha and IL-6 expression by rat hepatic macrophages (HM). As an in vivo model, cholestatic liver injury was induced in rats by ligation of the common bile duct (BDL). During the first 2 wk after BDL, there was an increase in the hepatic level of thiobarbituric acid-reactive substances (TBARS) that was accompanied by the appearance of protein-malondialdehyde adducts in the periportal region. This increase was reduced after 3 wk. TNF-alpha and IL-6 mRNA levels in HM from the BDL rats were increased at 1 and 2 wk and attenuated at 3 wk. Gel mobility shift assay of HM nuclear extracts demonstrated the similar temporal pattern of enhanced NF-kappa B binding activity. Treatment of the BDL animals with 1,2-dimethyl-3-hydroxypyrid-4-one (L-1), a lipophilic iron chelator, suppressed the increases in hepatic TBARS by 64%, plasma alanine aminotransferase by 45%, and HM TNF-alpha and IL-6 mRNA by > 84%. Concomitantly, the HM NF-kappa B binding activity was reduced close to the level observed in sham-operated rats. Treatment of cultured HM with L-1 also blocked lipopolysaccharide-stimulated NF-kappa B activation and TNF-alpha and IL-6 expression at mRNA and protein levels. These results demonstrate that the iron chelator effectively blocks NF-kappa B activation and coordinate TNF-alpha and IL-6 gene upregulation by HM in cholestatic liver injury or under in vitro lipopolysaccharide stimulation. These findings support a pivotal role for iron in activation of NF-kappa B and cytokine gene expression by HM in vitro and in vivo.
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PMID:Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages. 922 70

The study was conducted to investigate the impact of intestinal helminthiasis and treatment on iron status and acute phase response (APR) among urban Indonesian primary school children, aged 8-11 years old. The prevalence of helminthiasis among these children was; Ascaris lumbricoides, 81.6%; Trichuris trichiura, 88.3%; and mixed infection of A. lumbricoides and T. trichiura, 70.0%. Of 120 children enrolled in the investigation, 59 received a single 400 mg dose of albendazole, and 61 received a placebo. Ten days following treatment, the prevalence of ascariasis and trichuriasis in the treatment group diminished to 0% and 27%, respectively, and in the placebo group to 63.9% and 68.9%. Plasma iron, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) concentrations were determined prior to the intervention and 10 days after. Plasma iron concentrations and WBC count rose in the treatment group (p=< or =0.05) when compared to baseline status. Increases in hemoglobin concentrations observed in the treatment group 10 days post-treatment were not statistically significant. CRP, IL-1, IL-6 and TNF were found to be within normal limits for both groups both before and after treatment. ESR increased significantly in both treatment and placebo groups when compared the rates measured before treatment. These findings show that treatment with albendazole is associated not only with a decreased worm burden in school children, but also a rise in plasma iron.
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PMID:Anthelminthic treatment raises plasma iron levels but does not decrease the acute-phase response in Jakarta school children. 925 78

The aim of this study was to investigate the serum levels of interleukin-2 (IL-2) and interleukin-6 (IL-6) in children with iron deficiency anemia before and after iron supplementation. Twenty-five children with iron deficiency anemia 6 months to 3 years of age were included in the study. Ten age- and sex-matched healthy children constituted the control group. In the iron-deficiency group the production of IL-2 was found to be significantly lower than that in controls and became normal after iron supplementation (P < .001). But there was no difference in serum levels of IL-6 in iron deficiency anemia before and after iron supplementation (P > .05).
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PMID:Serum interleukin-2 and interleukin-6 levels in iron deficiency anemia. 950 8

To investigate the influence of functioning on unexplained senile anemia, we measured commonly used hematological parameters (serum iron, transferrin, iron saturation and ferritin) in addition to specific erythropoietic factors, such as interleukin-3 (IL-3), interleukin-6 (IL-6), and erythropoietin (EPO) in 48 elderly subjects aged 65-90 years. The subjects were divided into 3 groups: 1) 17 patients with unexplained mild anemia; 2) 17 non-anemic patients with newly acquired stroke and who previously were functionally active; 3) 14 functionally active patients with no major disease who served as controls. Anemia was defined as hemoglobin (Hb) values under 12.0 g/dL. The degree of functional ability was defined and scored by the "functional independence measure" (FIM) test. Data are presented as mean values +/- SD. The results revealed a correlation between the functional state and levels of Hb, iron and transferrin with unchanged iron saturation. Patients in the mild anemia group were found to be functionally declined (FIM = 57 +/- 19.4) with the relatively lowest mean iron (75.1 +/- 17 micrograms/dL) and transferrin levels (243 +/- 42.6 micrograms/dL). The stroke group (FIM = 62 +/- 17.7) had intermediate levels of iron (85.4 +/- 20.3 micrograms/dL) and transferrin (245 +/- 45.2), and with the continuation of the declined functional state the Hb level decreased significantly (13.7 +/- 0.9 to 12.0 +/- 1.0 g/dL, p < 0.001). The highest mean values of iron (102 +/- 27.9 micrograms/dL) and transferrin (322 +/- 42.7 micrograms/dL) were found in the control group (FIM = 122.7 +/- 5.8). The ferritin levels showed an opposite trend. IL-3 values were undetectable in the anemic and control groups, and were elevated in some patients in the stroke group. The lowest IL-6 level was observed in the anemic group, and the highest in the control group. Serial IL-6 assays in the stroke group showed an upward trend. Erythropoietin levels in all groups showed no difference.
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PMID:Relationship between routine hematological parameters, serum IL-3, IL-6 and erythropoietin and mild anemia and degree of function in the elderly. 958 49

Transgenic mice, named GFAP-IL6, that express interleukin-6 in astrocytes in the central nervous system (CNS) have a constitutive blood-brain barrier (BBB) defect and develop a progressive neurodegenerative disease. Based on ultrastructural observations showing electron-dense pigment in the brain of the GFAP-IL6 mice, we hypothesized that iron metabolism was altered in the brains of these animals. Enhanced histochemical methods revealed abnormal iron deposition in the cerebellum from 1 month of age that worsened with progression of the disease. Immunohistochemical analysis of iron-binding proteins (IBP) showed increased ferritin immunoreactivity and a decreased signal from the transferrin receptor in symptomatic animals. Atomic absorption spectroscopy revealed a 40% increase of total iron concentration in the cerebellum at the symptomatic stage. In order to obtain evidence that accumulation of this oxidizing metal was toxic, we looked for the presence of oxidative damage. Using the MAL-2 antibody, extensive lipid peroxidation (LP) was detected in the neocortex and the cerebellum in symptomatic animals. Ultrastructural analysis indicated lipofuscin deposition at the sites of neuro-axonal degeneration and abnormal iron deposition. These results suggest that the IL6-induced BBB defect precipitates iron accumulation in the GFAP-IL6 mouse brain and that subsequent IBP regulation mediates protective responses. As these defenses become overwhelmed, the iron overload seems to promote LP, which may contribute to the neurodegeneration that ensues. This transgenic mouse model of IL6-mediated neurodegeneration provides a unique opportunity to examine several aspects of iron metabolism in the brain, including its entry at the site of the BBB, its distribution through the IBP, and its mechanisms of toxicity.
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PMID:Abnormal iron deposition associated with lipid peroxidation in transgenic mice expressing interleukin-6 in the brain. 960 Feb 19

Oral exposure to chlorpyrifos (CHP) in the rat results in an initial hypothermic response followed by a delayed fever. Fever from infection is mediated by the release of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor (TNF alpha). This study determined if the CHP-induced fever involves cytokine-mediated mechanisms similar to that of infectious fevers. Long-Evans rats were gavaged with the corn oil vehicle or CHP (10-50 mg/kg). The rats were euthanized and blood collected at various times that corresponded with the hypothermic and febrile effects of CHP. Plasma IL-6, TNF alpha, cholinesterase activity (ChE), total iron, unsaturated iron binding capacity (UIBC), and zinc were measured. ChE activity was reduced by approximately 50% 4 h after CHP. There was no effect of CHP on IL-6 when measured during the period of CHP-induced hypothermia or fever. TNF alpha levels nearly doubled in female rats 48 h after 25 mg/kg CHP. The changes in plasma cytokine levels following CHP were relatively small when compared to > 1000-fold increase in IL-6 and > 10-fold rise in TNF alpha following lipopolysaccharide (E. coli; 50 microg/kg; i.p.)-induced fever. This does not preclude a role of cytokines in CHP-induced fever. Nonetheless, the data suggest that the delayed fever from CHP is unique, involving mechanisms other than TNF alpha and IL-6 release into the circulation characteristic of infectious fevers.
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PMID:Are circulating cytokines interleukin-6 and tumor necrosis factor alpha involved in chlorpyrifos-induced fever? 1041 84

Particulate matter (PM) metal content and bioavailability have been hypothesized to play a role in the health effects epidemiologically associated with PM exposure, in particular that associated with emission source PM. Using rat tracheal epithelial cells in primary culture, the present study compared and contrasted the acute airway epithelial effects of an emission source particle, residual oil fly ash (ROFA), with that of its principal constitutive transition metals, namely iron, nickel, and vanadium. Over a 24-h period, exposure to ROFA, vanadium, or nickel plus vanadium, but not to iron or nickel, resulted in increased epithelial permeability, decreased cellular glutathione, cell detachment, and lytic cell injury. Treatment of vanadium-exposed cells with buthionine sulfoximine further increased cytotoxicity. Conversely, treatment with the radical scavenger dimethylthiourea inhibited the effects in a dose-dependent manner. RT-PCR analysis of RNA isolated from ROFA-exposed rat tracheal epithelial cells demonstrated significant macrophage inflammatory protein-2 and interleukin-6 gene expression as early as 6 h after exposure, whereas gene expression of inducible nitric oxide synthase was maximally increased 24 h postexposure. Again, vanadium (not nickel) appeared to be mediating the effects of ROFA on gene expression. Treatment with dimethylthiourea inhibited both ROFA- and vanadium-induced gene expression in a dose-dependent manner. Corresponding effects were observed in interleukin-6 and macrophage inflammatory protein-2 synthesis. In summary, generation of an oxidative stress was critical to induction of the ROFA- or vanadium-induced effects on airway epithelial gene expression, cytokine production, and cytotoxicity.
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PMID:Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression. 1048 57

We hypothesized that the reduction in hospital respiratory admissions in the Utah Valley during closure of a local steel mill in 1986-1987 was attributable in part to decreased toxicity of ambient air particles. Sampling filters for particulate matter < 10 micrometer (PM(10)) were obtained from a Utah Valley monitoring station for the year before (year 1), during (year 2), and after (year 3) the steel mill closure. Aqueous extracts of the filters were analyzed for metal content and oxidant production and added to cultures of human respiratory epithelial (BEAS-2B) cells for 2 or 24 h. Year 2 dust contained the lowest concentrations of soluble iron, copper, and zinc and showed the least oxidant generation. Only dust from year 3 caused cytotoxicity (by microscopy and lactate dehydrogenase release) at 500 microgram/ml. Year 1 and year 3, but not year 2, dust induced expression of interleukin-6 and -8 in a dose-response fashion. The effects of ambient air particles on human respiratory epithelial cells vary significantly with time and metal concentrations.
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PMID:Effects of aqueous extracts of PM(10) filters from the Utah valley on human airway epithelial cells. 1056 81

The lack of backfiltration reduces plasma levels of C-reactive protein and interleukin-6. Paired filtration dialysis is the hemodialfitration technique that abolishes backfiltration. By physically separating convection from diffusion, it allows pure ultrafiltrate to be available during the entire session, so the ultrafiltrate can be regenerated and used as infusion fluid. On these premises, we have developed a European, open, randomised, multicentre study aimed at evaluating the effect of hemodiafiltration with on-line endogenous reinfusion (on-line HFR) on anemia. At least 130 chronically uremic hemodialysed (bicarbonate hemodialysis) stable patients with mild anemia (Hb between 9 and 11 g/dL) will be enrolled and normalized for iron stores by concomitantly repleting iron deposits (if ferritin <300 microg/L) and reducing the dose of erythropoietin to maintain Hb values within the range at enrollment (9-11 g/dL). Patients will be included in the study, randomized to the two treatments (test treatment: on-line HFR; control treatment: hemodiafiltration or modified forms) and followed up for nine months. Iron stores will be maintained within normal levels and the dose of erythropoietin will be kept constant. The primary question and response variable will be the mean monthly changes in hemoglobin levels over the period of nine months. As secondary questions and response variables, we will measure the nutritional status using a subjective global assessment, protein catabolic rate, urea generation rate and the dietician's assessment, serum concentrations of vitamins A, C, E and serum C-reactive protein.
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PMID:The effect of hemodiafiltration with on-line endogenous reinfusion (on-line HFR) on anemia: design of a European, open, randomised, multicentre trial. European Collaborative Study. 1072 Feb 12

Mineral particles in occupational exposure and ambient air particles may cause adverse health effects in humans. In this study the ability of different stone quarry particles to induce release of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) from human epithelial lung cells (A549) was investigated. Size distribution within the PM10 fractions was quite similar for all particle samples, whereas mineral content and metal composition differed. Particles, containing minerals such as quartz, amphibole, chlorite, and epidote, induced a marked increase in IL-6 and IL-8 release. Particles composed mainly of plagioclase were much less effective. The most potent particle samples exhibited a relatively high content of transition metals such as iron. Exposure to identical masses or surface areas resulted in the same order of potency among the different particle samples. Significant cytotoxicity was observed only at higher concentrations of particle exposure. Thus, mineral composition and/or metal contents of particles from different stone quarries were critical determinants for the marked differences in potency to induce cytokine responses in human epithelial lung cells.
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PMID:Mineral and/or metal content as critical determinants of particle-induced release of IL-6 and IL-8 from A549 cells. 1083 17


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