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)

The role of the immune system in the control of the production of erythropoietin is still poorly understood. Herein, the levels of circulating immunoreactive erythropoietin, tumour necrosis factor alpha, interleukin-1 beta and interleukin-6 were determined in 10 septic patients for up to 4 d following the admission to an internal intensive care unit. The data show that the production of erythropoietin was not suppressed despite an increase in the levels of proinflammatory cytokines. Circulating erythropoietin and interleukin-6 greatly increased in the 6 nonsurviving patients. The pattern of the serum erythropoietin level in the nonsurvivors resembled that of acute phase proteins and was independent of the blood haemoglobin concentration. Similar to interleukin 6, abnormally high serum erythropoietin levels appear to be a negative prognostic indicator in patients suffering from septic shock.
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PMID:Serum erythropoietin levels in patients with sepsis and septic shock. 900 76

Autologous blood transfusion is advantageous in that it eliminates the risk of transfusion-transmitted infection or complications caused by the immune reaction. Increased platelet counts after repeated phlebotomy are commonly observed. This study was carried out to clarify the mechanism of increased platelets during preoperative autologous blood donation. Eleven patients of elective surgery in which is in good preoperative condition and there is no emergency were selected for this study. Blood cell counts, platelet size distribution(PDW, MPV, P-LCR) and serum concentration of erythropoietin(EPO), interleukin-3(IL-3) and interleukin-6(IL-6)were measured. A transient increase in platelet was seen in almost patients during preoperative autologous blood donation. No marked changes in platelet size distribution and serum concentration of EPO, IL-3 and IL-6. These results suggest that increased platelet counts during preoperative autologous blood donation might be caused by some specific cytokines related to megakaryocyte differentiation such as c-MPL ligand.
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PMID:[Analysis of mechanism of increased platelet counts during preoperative autologous blood donation]. 902 46

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r = -0.54; P < 0.001; sTNF-R II: r = -0.47; P < 0.001) as well as interleukin-6 levels (r = -0.29; P < 0.01). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II (P < 0.01). The results of this study suggest that similar to its action in vitro, activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-alpha, this activation is particularly reflected by elevations of soluble TNF receptor levels.
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PMID:Inadequate erythropoietin response to anaemia in HIV patients: relationship to serum levels of tumour necrosis factor-alpha, interleukin-6 and their soluble receptors. 902 5

The recombinant hemopoietic factors of megakaryocyte potentiator (MEG-POT) were studied to compare their activity in stimulating proplatelet process formation (PPF) with thrombopoietin (TPO, c-MpI ligand). For the assay, a highly enriched (> 95%) population of more than 90% viable megakaryocytes was isolated from rat bone marrow using the immunomagnetic beads method and cultured with fetal calf serum (FCS) or in a serum-free condition. Megakaryocytes developing slender beaded cytoplasmic processes (proplatelet processes) were observed on both inverted phase contract microscopy and scanning electron microscopy. A large number of proplatelet process clusters were dose-dependently formed with the addition of varying doses of recombinant erythropoietin (rEpo) and interleukin-6 (rIL-6) as well as TPO. Epo and IL-6 were demonstrated to act synergistically solely at low doses in the development of PPF (P < 0.05). Other recombinant factors such as IL-11, leukemia inhibitory factor (LIF) and erythroid differentiation factor (EDF) appeared weak or ineffective. From these in vitro observations, it was suggested that a synergism of Epo and IL-6 might play a significant role in the terminal stage of megakaryocyte maturation leading to platelet release.
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PMID:Synergistic effects of erythropoietin and interleukin-6 on the in vitro proplatelet process formation of rat megakaryocytes. 911 Mar 49

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.
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PMID:An epidemiologic study of early biologic effects of benzene in Chinese workers. 911 21

The response of megakaryocytes and cytokines to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in monkeys with myelosuppression by carboplatin-treatment. Romurtide increased the number of megakaryocytes and promoted the shift of megakaryocytes towards high ploidy class indicative of the promotion of the proliferation and maturation of megakaryocytes. The serum levels of interleukin-6, stem cell factor, and erythropoietin elevated significantly before the enhanced response of megakaryocytes induced by romurtide was observed. Romurtide also enhanced production of colony-stimulating factors (CSFs), such as granulocyte-CSF, macrophage-CSF, and granulocyte-macrophage CSF by monkey mononuclear cells. The stimulating effect of romurtide on the production of those cytokines and CSFs is likely to be responsible for the subsequent promotion of the proliferation and maturation of marrow megakaryocytes.
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PMID:Romurtide, a synthetic muramyl dipeptide derivative, promotes megakaryocytopoiesis through stimulation of cytokine production in nonhuman primates with myelosuppression. 914 Dec 12

The median of survival among patients with multiple myeloma (MM) is about 30 months from the onset of treatment. Tumour burden and a range of other parameters, such as C-reactive protein levels, the plasma cell labelling index and beta2-microglobulin levels, can be used to assign patients to favourable and unfavourable prognostic groups. Conventional chemotherapy consists of melphalan and prednisone, and is as effective as moderately intensive cytotoxic drug regimens. Although second-line chemotherapy is initially effective, all patients eventually die. Maintenance therapy will interferon-alpha prolongs the plateau phase of the disease, but its effects on overall survival are minimal. One of the promising developments in the treatment of MM has been the introduction of high dosage chemotherapy, which can now be safely administered when stem cells are used for haematological recovery. Autologous bone marrow transplantation has been shown to produce a significant improvement in survival compared with conventional therapy. Several studies are under way that are examining the effects of multiple courses of high dosage chemotherapy together with peripheral stem cell support. Purging of autologous stem cell harvests will be performed in the near future to minimise contamination with myeloma cells. It is now feasible to use high dosage chemotherapy, with the support of granulocyte colony-stimulating factor-stimulated whole blood, in selected elderly patients. Besides the promising development of intensive therapy, a number of other treatment strategies have emerged, including treatment with monoclonal antibodies against interleukin-6 and multidrug resistance-modulating agents. Better supportive care can be provided for some patients by using epoetin (recombinant human erythropoietin), and the sequelae of lytic bone lesions can be ameliorated through the use of bisphosphonates.
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PMID:Treatment of multiple myeloma in elderly patients. New developments. 925 78

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

In an effort to expand human hematopoietic progenitors and stem cells in vitro, we cultured human CD34(+)c-kitlow bone marrow cells in suspension in the presence of KIT ligand, FLK2/FLT3 ligand, interleukin-6 (IL-6), and erythropoietin with or without IL-3 and tested their engrafting capabilities by injecting them into sheep fetuses. As markers for engraftment, we analyzed CD45(+) cells and karyotypes of the colonies grown in methylcellulose culture. In three separate experiments, day-60 engraftment in the bone marrow was seen with both fresh cells and cells cultured in the presence or absence of IL-3. When fetuses were allowed to be born and analyzed for CD45(+) cells, no long-term engraftment was seen with cultured cells. We then pooled the CD45(+) cells of the fetal samples and transplanted them into secondary recipient fetuses. Day-60 engraftment in the secondary recipients was again noted when transplantation in the primary recipients was initiated with fresh cells. There were 3 cases in which cultured cells showed signs of engraftment in the secondary recipients, but the remaining 24 cases showed no signs of engraftment. These data documented that suspension culture for 2 weeks of enriched adult human bone marrow cells can maintain short-term (2 months) engrafting cells, but may not maintain longer term engrafting cells. This sheep/human xenograft model may serve as an excellent method for the evaluation of the engraftment potential of in vitro-expanded cells.
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PMID:Engraftment of cultured human hematopoietic cells in sheep. 957 5

Cytokines produced by stromal cells induce the proliferation and differentiation of hematopoietic cells in the marrow microenvironment. We hypothesized that cross-talk between hematopoietic cells at different stages of differentiation and stromal cells influences stromal cytokine production and is responsible for maintaining steady-state hematopoiesis and responding to stress situations. We show that coculture of primitive CD34(+) cells in contact with or separated by a transwell membrane from irradiated human bone marrow stromal layers induces a fourfold to fivefold increase in interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) levels in the stromal supernatant (SN) during the first week. Levels of both cytokines decreased to baseline after coculture of CD34(+) cells for 3 to 5 weeks. Coculture of more mature CD15(+)/CD14(-) myeloid precursors induced only a transient 1.5- to 2-fold increase in IL-6 and G-CSF at 48 hours. Neither CD34(+) nor CD15(+)/CD14(-) cells produced IL-6, G-CSF, IL-1beta, or tumor necrosis factor alpha. When CD34(+) cells were cultured in methylcellulose medium supplemented with cytokines at concentrations found in stromal SN or supplemented with stromal SN, a fourfold to fivefold increase in colony formation was seen over cultures supplemented with erythropoietin (EPO) only. When cultures were supplemented with the increased concentrations of IL-6 and G-CSF detected in cocultures of stroma and CD34(+) cells or when CD34(+) cells were cocultured in methylcellulose medium in a transwell above a stromal layer, a further increase in the number and size of colonies was seen. The colony-forming unit-granulocyte-macrophage-stimulating activity of stromal SN was neutralized by antibodies against G-CSF or IL-6. These studies indicate that primitive CD34(+) progenitors provide a soluble positive feedback signal to induce cytokine production by stromal cells and that the observed increase in cytokine levels is biologically relevant.
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PMID:Human CD34(+) bone marrow cells regulate stromal production of interleukin-6 and granulocyte colony-stimulating factor and increase the colony-stimulating activity of stroma. 957 9


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