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)

To study the role of different cytokine combinations on the proliferation and differentiation of highly purified primitive progenitor cells, a serum-free liquid culture system was used in combination with phenotypic and functional analysis of the cells produced in culture. CD34+ CD45RAlo CD71lo cells, purified from umbilical cord blood by flow cytometry and cell sorting, were selected for this study because of their high content of clonogenic cells (34%), particularly multipotent progenitors (CFU-MIX, 12% of all cells). Four cytokine combinations were tested: (1) mast cell growth factor (MGF; a c-kit ligand) and interleukin-6 (IL-6); (2) MGF, IL-6, IL-3, and erythropoietin (Epo); (3) MGF, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-3 fusion protein (FP), macrophage colony-stimulating factor (M-CSF), and granulocyte-CSF (G-CSF); and (4) MGF, IL-6, FP, M-CSF, G-CSF, and Epo. Maximum numbers of erythroid progenitors (BFU-E, up to 55-fold increase) and mature erythroid cells were observed in the presence of MGF, IL-6, IL-3, and Epo, whereas maximum levels of myeloid progenitors (CFU-C, up to 70-fold increase) and mature myeloid cells were found in cultures supplemented with MGF, IL-6, FP, M-CSF, and G-CSF. When MGF, IL-6, FP, M-CSF, G-CSF, and Epo were present, maximum levels of both erythroid and myeloid progenitors and their progeny were observed. These results indicate that specific cytokine combinations can act directly on primitive hematopoietic cells resulting in significant expansion of progenitor cell numbers and influencing their overall patterns of proliferation and differentiation. Furthermore, the observations presented in this study suggest that the cytokine combinations used were unable to bias lineage commitment of multipotent progenitors, but rather had a permissive effect on the development of lineage-restricted clonogenic cells.
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PMID:Cytokine-induced selective expansion and maturation of erythroid versus myeloid progenitors from purified cord blood precursor cells. 768

Oncostatin M (OM) is structurally and functionally related to a subclass of hematopoietic cytokines including leukemia-inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6). Using human endothelial cells (HEC) as a model for cytokine regulation of hematopoietic growth factor expression, we tested OM as an inducer of colony-stimulating activity. Colony-forming cell assays supplemented with culture supernatants from OM-treated HEC contained a threefold increase in colony-forming unit granulocyte-macrophage colonies. Specific immunoassay (enzyme-linked immunosorbent assay) of culture supernatants indicated that OM treatment of HEC resulted in a dose- and time-dependent increase in the accumulation of G-CSF and granulocyte-macrophage CSF (GM-CSF) (> 28-fold). The ED50 for OM induction of G-CSF and GM-CSF protein expression was 17 and 7 pmol/L, respectively. Increased protein expression was associated with a similar increase in steady-state expression of G-CSF and GM-CSF mRNA. Furthermore, a period of 12 to 24 hours elapsed before there were measurable increases in CSF expression, suggesting that OM may stimulate CSF production through a mechanism requiring the synthesis or activation of a secondary mediating factor or pathway. These findings provide the first evidence that OM may regulate myelopoiesis by inducing the cellular expression of hematopoietic growth factors.
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PMID:Regulation of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor expression by oncostatin M. 768 88

To explore the pathogenesis of marrow failure in B-cell type chronic lymphocytic leukemia (B-CLL), we have examined the production of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage CSF (GM-CSF) by the adherent cell population of bone marrow (BM) derived from B-CLL patients and their capacity to support hematopoietic cell proliferation. Lipopolysaccharide-stimulated B-CLL stromal cells produced G-CSF and GM-CSF in amounts similar to normal stromal layers, whereas IL-6 production was significantly decreased. Using the blast-colony forming cell assay (BI-CFC) and the classical colony-forming unit granulocyte macrophage (CFU-GM) assay, we found that: (1) marrow stromal cells of B-CLL were able to support only 25% of the BI-CFC growth supported by normal marrow stromal cells; (2) this anomaly was partially corrected by the addition of exogenous IL-6; (3) the colony-stimulating activity (CSA) of the conditioned medium (CM) of B-CLL stromal cells was lower than that of normal CM; (4) that this was the result of the presence of an inhibitor rather that of a growth factor defect; (5) this inhibition could be abrogated by addition of anti-transforming growth factor-beta (TGF-beta) neutralizing antibody; (6) this antibody corrected the deficient colony supportive activity of the B-CLL stromal cells; (7) TGF-beta production by marrow stromal cells was significantly increased in CLL compared with normal; and (8) that this was not caused by the effect of the B-CLL lymphocytes on the stromal cells. It is concluded that this increased TGF-beta production in B-CLL is probably responsible for the decreased IL-6 production by stromal cells and for the inhibiting activity on hematopoietic precursors as well. We hypothesize that TGF-beta generated at a high level by B-CLL marrow stromal cells could play a major role in the pathophysiology of the BM failure seen in advanced stages of B-CLL.
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PMID:Excessive production of transforming growth factor-beta by bone marrow stromal cells in B-cell chronic lymphocytic leukemia inhibits growth of hematopoietic precursors and interleukin-6 production. 769 Dec 58

In this study, we investigated the effect of recombinant human interleukin-6 (IL-6) on colony-forming cells for granulocytes and macrophages (CFU-GM) cultured in suspension. IL-6 when used alone did not induce proliferation of highly purified CD34+ human hematopoietic progenitors. Moreover, no influence of IL-6 was observed on the proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte (G)-CSF. However, a marked survival enhancement (GM-CSF 228 +/- 42%, p < 0.01, and G-CSF 137 +/- 9%, p < 0.05) was observed when CD34+ cells were preincubated with IL-6 for 6 days. This survival effect became even more pronounced under serum-poor conditions (GM-CSF 380 +/- 80%, p < 0.01, and G-CSF 180 +/- 20%, p < 0.01) and could also be demonstrated at the single cell level in a colony-forming assay. By analysis of subpopulations of CD34+ bone marrow (BM) cells selected on the basis of CD45RO expression, the observed IL-6-mediated survival effect was found to be restricted to the CFU-GM containing CD45RO- subset. Our data show that IL-6 is a survival factor for CFU-GM.
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PMID:Interleukin-6 is a survival factor for committed myeloid progenitor cells. 769 39

It has been hypothesized that interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) may fold as four-alpha-helix bundle proteins. To probe the functional role of the putative fourth helical segment of IL-6 (D-helix), a chimeric IL-6/G-CSF analog containing the predicted D-helix of G-CSF as well as a panel of IL-6 D-helix point mutants were analyzed for their respective secondary structure, antigenicity, and receptor binding and biological activities. The putative D-helix of IL-6 could not be replaced by its G-CSF counterpart in spite of their high degree of similarity and thus is indispensable for the antigenic and functional integrity of the IL-6 receptor binding site. Conversely, the grafting of the G-CSF D-helix did not confer any G-CSF activity to IL-6. A synthetic helical peptide containing the IL-6 D-helix was inactive, even when mixed with or linked to a peptide from the A-helix known to be involved in the active site. However, the conserved residues F173, R179, and R182 found in the D-helices of both IL-6 and G-CSF critically contribute to the architecture of the IL-6 active site. Indeed, mutation of F173 or R179 markedly affected IL-6 receptor binding and biological activities, but not the conformation of a major neutralization epitope. Furthermore, substitution of R182 resulted in a significant unfolding of the D-helix accompanied by a drastic loss in IL-6 antigenicity and functional activities. Nevertheless, residues other than F173, R179, and R182 also contribute to IL-6 specificity.
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PMID:Structure-function analysis of the C-terminal segment of human interleukin-6. 769 65

A young Italian woman with a POEMS syndrome is described. The patient had a plasma cell dyscrasia without clinical or laboratory evidence of multiple myeloma. The phenotypic analysis of bone marrow cells and peripheral blood lymphocytes revealed a normal pattern. The immunological study of CSF showed high levels of interleukin-6, whereas this cytokine was not detectable in the serum. Electrophysiological studies and sural nerve biopsy showed a mixed, demyelinating-axonal sensorimotor neuropathy with marked loss of large myelinated fibres. Long-term treatment with prednisone gave some clinical improvement.
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PMID:POEMS syndrome: clinical, pathological and immunological study of a case. 770 42

Recent investigations have revealed the involvement of cytokines in the pathogenesis of psoriasis. This study examined the amount of inflammatory cytokines--interleukin-1 (IL-1), interleukin-6 (IL-6) and granulocyte macrophage colony-stimulating factor (GM-CSF)--released into the supernatants of organ cultures of involved and uninvolved skin from psoriatic patients and normal skin from healthy individuals. Bioassays were employed to detect the activities of IL-1 and IL-6. Enzyme-linked immunosorbent assay (ELISA) methods were used to quantitate immunoreactive IL-1 alpha, IL-1 beta, IL-6 and GM-CSF. The activity of IL-1 in uninvolved psoriatic skin was found to be increased relative to that in involved and normal skin, while immunoreactive IL-1 beta was found only in involved skin. A neutralization experiment showed that bioactive IL-1 was mostly attributable to IL-1 alpha. Uninvolved psoriatic skin also secreted higher amounts of both bioactive and immunoreactive IL-6 compared with involved skin. Immunoreactive GM-CSF was detected in uninvolved skin only. These cytokines detected in uninvolved skin may have been released from epidermal or mesenchymal cells, since uninvolved skin contained fewer inflammatory infiltrates. Our results offer additional evidence that increased amounts of inflammatory cytokines in uninvolved skin may provide a preliminary condition and play important roles in the initial events in the evolution of psoriatic lesions.
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PMID:Detection of inflammatory cytokines in psoriatic skin. 776 87

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor Tb continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21 degrees C reached by 3.7 +/- 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in Tb of 1.2 +/- 0.25 degrees C, 1.8 +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees C and duration of 6.2 +/- 1.28 hr, 6.7 +/- 0.49 hr, and 6.8 +/- 0.65 hr when given in doses of 25, 50, and 100 ng, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1 beta (MIP-1 beta). 780 90

The synthesis and release of parathyroid hormone-related protein (PTHrP) could be influenced in a paracrine or autocrine manner by substances present around or inside tumours, such as bone or stromal cell-derived cytokines, factors produced by the tumour itself or by peritumoural inflammatory cells. We investigated the effects of various cytokines known to be synthesized by osteoblasts, stromal cells, leucocytes or cancer cells, on PTHrP production by the human lung squamous cell carcinoma line BEN. The influence of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was studied, and compared with those of insulin-like growth factors-I and -II (IGF-I, IGF-II), or macrophage- or granulocyte-macrophage colony-stimulating factors (M-CSF, GM-CSF). TNF-alpha caused a 1.9 +/- 0.1-fold increase in immunoreactive PTHrP production, which was maximal by 24 h of incubation. IL-6 caused a 2.3 +/- 0.2-fold increase, which was maximal by 16 h. These effects, which were time- and concentration-dependent, were blocked by monoclonal antibodies raised against the corresponding cytokine. An increase of PTHrP mRNA was found in IL-6-treated cells. IGF-I and IGF-II increased PTHrP production by 2.0 +/- 0.3- and 2.3 +/- 0.1-fold respectively. Neither M-CSF nor GM-CSF altered PTHrP production up to 64 h of incubation. PTHrP production was not affected by varying extracellular calcium concentrations, but was decreased by incubation with 100 nmol/l dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of parathyroid hormone-related protein production in a human lung squamous cell carcinoma line. 782 96

Interleukin-6 (IL-6) can alter brain function after peripheral administration, suggesting that it, like IL-1 alpha, IL-1 beta and TNF-alpha, might be able to cross the blood-brain barrier (BBB). We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) into brain of radioactively labeled murine and human IL-6 given i.v. Ki values ranged from 3.05 to 4.54 (10(-4)) ml/g/min and were inhibited by unlabeled IL-6 but not IL-1 alpha or TNF-alpha, showing that the transport system for IL-6 is distinct from those for IL-1 alpha and TNF-alpha. Approximately 0.2% of the dose injected i.v. entered each gram of brain. The capillary depletion method showed that most of the IL-6 taken up by brain entered the parenchyma. However, only approximately 16% of the radioactivity recovered eluted as intact I-IL-6 in brain and approximately 50% in CSF after chromatographic separation by HPLC/Sephadex. The efflux rate for IL-6 injected into the lateral ventricle of the brain suggests that it enters the blood with the reabsorption of CSF. These results suggest that blood-borne IL-6 can reach sites behind the BBB, but that susceptibility to enzymatic degradation may limit contact time within the CNS.
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PMID:Penetration of interleukin-6 across the murine blood-brain barrier. 784 24


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