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)

Transcobalamin (TCII) and haptocorrins (TCI and III), tumour necrosis factor alpha (TNF), interleukin-6 (IL6) and parameters of disease activity were assessed in 20 rheumatoid arthritis (RA) patients without anaemia and 19 subjects with anaemia of chronic disease (ACD) in order to determine if there was a possible correlation between these parameters. TCII, TNF and IL6 correlated positively with RA disease activity parameters, whereas their serum levels were higher in the ACD patients. TC levels were not correlated with cytokine levels. Vitamin B12 serum levels were lower in ACD. We conclude that in RA, elevated serum TCII levels are possibly mediated by increased RA disease activity, but probably not by actions of TNF or IL6. Increased TCII levels found in ACD may be explained by the higher degree of RA activity in these patients, and could also be viewed as a compensatory reaction to anaemia or reduced vitamin B12 levels. However, these preliminary findings require further confirmation.
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PMID:Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6. 160 92

Serum and bone marrow from 21 patients with rheumatoid arthritis (RA) were studied in order to establish the pathogenetic role of interleukin-6 (IL-6) in anemia of chronic disease (ACD). Erythroid colony growth, using burst forming units of erythroblasts (BFUe) as a parameter, was impaired in ACD and not in nonanemic RA controls. Serum IL-6 was elevated in ACD and it correlated well with parameters of disease activity such as erythrocyte sedimentation rate and C-reactive protein. IL-6 addition to bone marrow cultures had inconsistent effects while anti-IL-6 addition resulted in impaired erythroid colony growth, suggesting stimulatory effects of IL-6 produced in the medium, which may be masked by simultaneous production of cytokines with suppressive effects. It was concluded that elevated serum IL-6 in ACD reflects disease activity. It probably plays no pathogenetic role in ACD. Its stimulatory effects on erythroid growth might counteract suppressive effects of other interleukins.
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PMID:Anaemia of chronic disease in rheumatoid arthritis. Raised serum interleukin-6 (IL-6) levels and effects of IL-6 and anti-IL-6 on in vitro erythropoiesis. 239 39

Erythropoiesis is controlled by different regulators. Interleukin 3, granulocyte-macrophage colony-stimulating factor and stem cell factor play regulatory functions in the early steps of erythropoiesis. Erythropoietin (Epo) is the main factor which acts positively on the last steps of the production of erythrocytes in mammals. Epo is specific for the erythroid progenitor cells and has only little effect on other cells. The target cells for Epo are the erythroid progenitors (BFUe and CFUe). Epo acts on these progenitors through surface receptors specific for Epo. Epo induces the proliferation and differentiation of erythroid progenitors leading finally to reticulocytes. During this process, certain conditions are required to permit this differentiation: progenitors must be present in sufficient numbers, the bone marrow environment must be normal, and nutrients such as folic acid, vitamin B12 and particularly iron must be available. Elemental iron is an absolute requirement for adequate haemoglobin formation. Indeed, in a normal adult, without any stimulation, the bone marrow synthesizes 4 x 10(14) molecules of haemoglobin per second, each molecule containing four atoms of iron, which roughly corresponds to 20 mg iron. On the other hand, erythropoiesis is negatively regulated by several cytokines. These are macrophage-derived cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta). All these factors are elevated in the inflammatory state and are implicated in the pathogenesis of anaemia of chronic disease. TNF-alpha has an inhibitory effect on erythroid progenitors either directly or mediated by interferon-beta (INF-beta). IL-1 inhibits erythropoiesis in vivo in mice and in vitro in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular mechanism of resistance to erythropoietin. 852 90

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.
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PMID:Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. 863 55

Anaemia of chronic disease (ACD) is a common feature of active rheumatoid arthritis (RA). Inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), are thought to contribute to the pathogenesis of ACD, possibly by inhibiting erythropoietin (EPO) production. In this study, we examined the in vivo effects of TNF-alpha blockade with a chimeric monoclonal antibody, cA2, on erythropoiesis in RA patients with ACD. Administration of cA2 led to a dose-dependent increase in haemoglobin levels compared to placebo and these changes were accompanied by a reduction in both EPO and IL-6 levels. The data support the notion that TNF-alpha is important in the causation of ACD, but suggest a mechanism independent of EPO suppression. Instead, TNF-alpha may act directly on bone marrow red cell precursors.
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PMID:Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade. 937 90

The aim of our study was to evaluate the role of proinflammatory cytokines: tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), as well as the possible contribution of interleukin-10 (IL-10) in anemia of chronic disease (ACD) of rheumatoid arthritis (RA) patients. We measured the serum levels of TNFalpha, IL-1beta, and IL-6 in 105 anemic and 127 nonanemic RA patients. We also investigated the effects of the above cytokines on the development of burst-forming units-erythroid (BFUe) and colony-forming units-erythroid (CFUe) in bone marrow cultures. Anemic patients had significantly higher serum levels of TNFalpha, IL-1beta, and IL-6 compared to nonanemics. Serum IL-10 levels were low and there was no significant difference in IL-10 concentrations between anemic and nonanemic patients. Proinflammatory cytokines inhibited proliferation of BFUe and CFUe. IL-10 did not decrease the erythroid colony growth. Proinflammatory cytokines may play a role in the pathogenesis of ACD in RA patients. Low levels of IL-10 possibly contribute to the development of ACD.
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PMID:Role of cytokines in the pathogenesis of anemia of chronic disease in rheumatoid arthritis. 1044 59

The influence of interleukin-6 (Il-6) on human erythropoietic progenitors growth in vitro was evaluated. It was found Il-6 causes approximately 35% inhibition of early BFU-E growth stimulated with erythropoietin, kit ligand and interleukin-3, Il-6 did not inhibit erythroid colony formation by late BFU-E and CFU-E progenitors. This data suggests the role Il-6 as one of inflammatory cytokines in pathogenesis of anemia of chronic disease acting inhibitory at early BFU-E erythroid progenitors level.
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PMID:[In vitro studies on anemia in chronic inflammatory disease: influence of interleukin-6 on human erythropoietin]. 1090 20

Changes in hemoglobin (HGB) and serum albumin (SA) concentration associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing the values obtained on the day thalidomide or prednisone therapy commenced, with each patients' preceding values. In three groups of ENL patients mean HGB values fell with statistical significance: 1) in 38 patients who had been begun on thalidomide in the decade of the 1990s and who had been receiving dapsone for a minimum of 6 months, mean HGB values fell from 13.19 gm/dl to 12.27 gm/dl, or 7.0%, p = 6.0 x 10(-6); 2) in 8 patients who were in the active patient file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean HGB values feel from 13.40 gm/dl to 11.96 gm/dl, or 10.7%, p = 0.0015; and 3) in 8 patients not overlapping with the preceding groups, who were treated with rifampin and minocylcine or clarithromycin mean HGB values fell from 13.25 gm/dl to 12.48 gm/dl, or 5.8%, p = 0.0035. In two groups of ENL patients SA values also fell with statistical significance: 1) in 34 patients who were begun on thalidomide in the decade of the 1990s and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.14 gm/dl to 3.77 gm/dl, or 8.9%, p = 1.2 x 10(-5); and 2) in 10 patients from the active file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.45 gm/dl to 4.06 gm/dl, or 8.8%, p = 0.039. A brisk fall in HGB values was often accompanied by a fall in SA concentration, and vice versa. Recovery from extreme falls in HGB and SA values was complete in 13 weeks. Recovery occurred in the presence of continued dapsone treatment. The falls could be rapid, occurring too soon to be the result of decreased erythropoiesis or hepatic SA synthesis. This study provides no direct evidence as to the mechanism responsible for the fall in these two parameters, but an interleukin-6 mediated hemodilution is an attractive hypothesis. The ENL-associated fall in HGB values was distinct from dapsone-induced hemolysis and the anemia of chronic disease. The ENL-associated anemia is not a good reason to discontinue dapsone therapy.
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PMID:Decreases in mean hemoglobin and serum albumin values in erythema nodosum leprosum and lepromatous leprosy. 1203 93

Anemia of chronic disease (ACD) is a condition of decreased red cell mass secondary to some other chronic inflammatory condition. In ACD total body iron stores are normal, though serum iron is typically low secondary to iron sequestration by macrophages, and often iron supplementation is not an effective treatment for ACD for the same reason. The pathogenesis of ACD had been poorly understood, but recently there has been important progress: upregulation of interleukin-6 (Il-6) secondary to the underlying chronic inflammatory disease upregulates expression of the protein hepcidin. Upregulation of hepcidin causes anemia by a number of mechanisms: decreased intestinal absorption of iron from the duodenum, increased sequestration of iron by macrophages. Thus, downregulation of Il-6 may represent a most important treatment avenue for ACD. Anti-Il-6 antibodies might be a way to lower Il-6 levels, but such antibodies besides being expensive would have to be given intravenously or intramuscularly, and such large immunogenic molecules may not be appropriate in patients already with a chronic inflammatory condition. Here, we note that an immediately available and potentially effective treatment for ACD is to decrease Il-6 levels by histamine (H1) receptor antagonism, given that histamine acting through the H1 receptor is known to be a potent positive regulator of Il-6. Among the classes of medications that are H1 antagonists we point out that atypical antipsychotic medications such as olanzapine and quetiapine are among the most potent H1 antagonists, and can have simple daily dosing schedules and thus may be particularly useful in ACD.
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PMID:Using histamine (H1) antagonists, in particular atypical antipsychotics, to treat anemia of chronic disease via interleukin-6 suppression. 1589 20

Anemia of chronic disease (ACD) is commonly observed in chronic inflammation, although its pathogenesis is poorly understood. Hepcidin is thought to be a key regulator in iron metabolism and has been implicated in ACD. Although the induction of hepcidin by an inflammatory cytokine interleukin-6 (IL-6) seems to have been confirmed, it is still controversial whether interleukin-1beta (IL-1beta), also known as an inflammatory cytokine, regulates hepcidin expression. We demonstrated that hepcidin mRNA was upregulated by IL-1beta in human hepatoma-derived HuH-7 cells, particularly at low concentrations of IL-1beta, while high concentrations of IL-6 were needed for the upregulation of hepcidin mRNA. Therefore, IL-1beta might be more important for the upregulation of hepcidin in physiological conditions than IL-6. Although IL-1beta induces IL-6 production in hepatocytes, our data indicate that the effect of IL-1beta on hepcidin expression is independent from that of IL-6. In conclusion, IL-1beta might have an important role in ACD.
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PMID:Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines. 1619 22


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