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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetic profile of cytokine gene expression in normal human peripheral mononuclear cells (MNC) activated by an anti-CD3 monoclonal antibody was studied. The presence or absence of 10 different cytokine mRNA were measured in a polymerase chain reaction (PCR) assisted mRNA amplification assay. After 2 h of stimulation the mRNA for interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were detectable and remained present during the whole time period studied (22 h). Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were detected after 4 h, while interleukin-10 (IL-10) mRNA did not appear until after 7 h; they all remained expressed at 22 h. A transient expression of interleukin-4 (IL-4) mRNA was observed between 4 and 7 h of stimulation. No gene expression of granulocyte colony stimulating factor (G-CSF) was detected at any time. These results show that anti-CD3 stimulation of MNC leads to a rapid sequential induction of different cytokine mRNA, some with a very transient expression.
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PMID:OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction. 143 86

The interactions of purified recombinant human leukemia inhibitory factor (LIF), interleukin-6 (IL-6), granulocyte colony stimulating factor (G-CSF), and granulocyte-macrophage CSF (GM-CSF) on the clonogenicity of HL60 cells and U937 cells were studied in vitro. IL-6 alone strongly suppressed colony formation by U937 cells with induction of differentiation and loss of clonogenicity. GM-CSF interacted synergistically with IL-6 to further reduce colony number and suppress the growth of clonogenic cells formed by HL60 and U937 cells. LIF synergized with IL-6 to reduce colony number and enhance the suppression of the clonogenic U937 cells. The results suggest that these 4 glycoproteins, acting alone or in combination, may be able to suppress human leukemia cells of appropriate type and be of value in the clinical management of myeloid leukemia.
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PMID:Enhanced suppression of human myeloid leukemic cell lines by combinations of IL-6, LIF, GM-CSF and G-CSF. 168 77

Purified recombinant granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) stimulated the formation of similar numbers of colonies in cultures of normal mouse marrow cells. LIF and IL-6 induced comparable differentiation in clonal cultures of murine M1 leukemic cells and exhibited enhanced actions in combination. However, LIF was 16-25-fold more active than IL-6. Induction of differentiation in M1 leukemic colonies by both LIF and IL-6 was enhanced by the addition of G-CSF or M-CSF but not by GM-CSF or Multi-CSF. Both G-CSF and IL-6, but not LIF, were able to induce differentiation in murine WEHI-3B leukemic colonies, but G-CSF was 10-fold more efficient than IL-6. Both G-CSF and IL-6 were able to stimulate the proliferation of cells of the NFS-60 continuous cell line, but G-CSF was 30-fold more efficient. M1 cells constitutively produced low levels of IL-6 and production was enhanced by LIF, but the general characteristics of the actions of LIF, IL-6, and G-CSF suggested that each operates independently as a direct differentiation inducer of leukemic cells. The similarities in the biology and actions of G-CSF, LIF, and IL-6 suggest that they may be designed to exhibit coordinated biological functions in certain situations.
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PMID:Actions and interactions of G-CSF, LIF, and IL-6 on normal and leukemic murine cells. 246 11

The amino acid sequences of human interleukin-6 and granulocyte colony stimulating factor are approximately 30% homologous in the N-terminal region. The relative positions of four half-cystines in human interleukin-6 (IL-6) match four of the five in human granulocyte colony stimulating factor. Labeling experiments of recombinant interleukin-6 with tritiated iodoacetate confirmed that the molecule forms two intramolecular disulfide bonds and contains no detectable level of free sulfhydryls. By isolation and characterization of tryptic and subtilytic peptides obtained from different proteolytic digestions, the disulfide bonds of the IL-6 molecule were assigned to Cys44-Cys50 and Cys73-Cys83. The two disulfide bridges form two small loops which are separated by 22 amino acids. These structures are similar to those of recombinant granulocyte colony stimulating factor.
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PMID:Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor. 247 17

Interleukin-6 (IL-6) drives the sequential assembly of a receptor complex formed by the IL-6 receptor (IL-6R alpha) and the signal transducing subunit, gp130. A model of human IL-6 (hIL-6) was constructed by homology using the structure of bovine granulocyte colony stimulating factor. The modeled cytokine was predicted to interact sequentially with the cytokine binding domains of IL-6R alpha and gp130 bridging them in a way similar to that of the interaction between growth hormone and its homodimeric receptor. Several residues on helices A and C which were predicted as contact points between IL-6 and gp130 and therefore essential for IL-6 signal transduction, were subjected to site-directed mutagenesis individually or in combined form. Interestingly, while single amino acid changes never produced major alterations in IL-6 bioactivity, a subset of double mutants of Y31 and G35 showed a considerable reduction of biological activity and were selectively impaired from associating with gp130 in binding assays in vitro, while they maintained wild-type affinity towards hIL-6-R alpha. More importantly, we demonstrated the antagonistic effect of mutant Y31D/G35F versus wild-type IL-6.
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PMID:Generation of interleukin-6 receptor antagonists by molecular-modeling guided mutagenesis of residues important for gp130 activation. 751 Nov

The physiologic program of macrophage differentiation normally proceeds in a coordinated manner in response to several different growth factors. Although the utilization of common receptor subunits may explain in part overlapping biologic functions, mechanisms by which unique actions are mediated remain obscure. We examined growth factor-induced macrophage differentiation in M1 leukemia cells that simultaneously display receptors for interleukin-6 (IL-6), leukemia inhibitory factor (LIF) and Oncostatin-M (OSM). Differentiation induced by all three factors was associated with decreased expression of transcription factors myb and SCL, increased expression of macrophage markers, and suppression of proliferation. Cell lines were established in which SCL expression was enforced. In the absence of growth factors, cells were indistinguishable from parental cells. However, LIF (or OSM)-induced macrophage differentiation was perturbed; there was failure to undergo morphologic differentiation, disturbed expression of lysozyme and Mac1 alpha, and failure to suppress proliferation. Surprisingly the perturbation of macrophage differentiation did not apply to induced expression of macrophage colony-stimulating factor (M-CSF) or granulocyte colony stimulating factor (G-CSF) receptors. This dissociation of elements normally coordinated in a macrophage differentiation program applied at a clonal level. There was no disturbance of IL-6-induced macrophage differentiation. These data directly implicate SCL in components of the macrophage differentiation program (suggesting that LIF receptor/gp130 heterodimers utilize an SCL-inhibitable pathway while gp130 homodimers do not) and demonstrate differential-regulation of components of the mature macrophage phenotype.
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PMID:Differential regulation of macrophage differentiation in response to leukemia inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression of the SCL transcription factor. 781 94

Human interleukin-11 (IL-11) is a cytokine with a broad spectrum of activity, similar to interleukin-6 (IL-6). However, its role in human disease is poorly understood, partly because of a lack of sensitive bioassays. A subclone (B9-11) obtained from the B9 hybridoma (which responds poorly to human IL-11) enabled us to develop a highly sensitive bioassay for human IL-11. B9-11 cells responded only to human IL-11 and IL-6 and not to other human cytokines using the same gp130 transducer chain (ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M) or to other human interleukins (interleukin-1 to interleukin-13), human hematopoietic cytokines (granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, colony stimulating factor-1) and various other human cytokines (interferon-alpha, tumor necrosis factor-alpha, tumor necrosis factor-beta, fibroblast growth factor and nerve growth factor). In addition, these cytokines did not interfere with the IL-11 response of B9-11 cells. IL-11-induced proliferation of B9-11 cells was unaffected by anti-murine IL-6 receptor mAb but inhibited by anti-gp130 mAb. Half-maximal proliferation of B9-11 cells was obtained with 30 pg/ml of recombinant IL-11, a concentration 300-fold lower than IL-11 concentrations known to be active on human cells. Finally, culturing of B9-11 cells with an anti-IL-6 mAb enabled us to measure the natural IL-11 produced by various cell lines. Thus, B9-11 cells should be useful for studies of IL-11 involvement in various human diseases as well as for a better understanding of the mechanisms of action of this cytokine.
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PMID:A highly sensitive quantitative bioassay for human interleukin-11. 803 82

The authors have evaluated adhesive protein expression and cytokine production by human umbilical vein endothelial cells cultured in contact with polyethylene terephthalate (PET). ELAM-1, ICAM-1 and VCAM-1 expression was determined by flow cytometry; the concentration of interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the supernatant was determined by enzyme immunoassay. The contact with PET determined a significant increase in ELAM-1 expression and insignificant increase in cytokine production, demonstrating that PET had a limited capability to stimulate endothelial cells in a pro-inflammatory sense.
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PMID:Cytokine production and adhesive protein expression by endothelial cells after contact with polyethylene terephthalate. 890 40

Conventional outcomes research provides only percentage risk categories that are not applicable to individual patients, and it predicts only mortality, utilization of resources and/or broad groupings of multiple organ system dysfunction. The purpose of the present study was to determine whether or not the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic parameters, standard hospital laboratory tests, and circulating cytokine concentrations to predict continuous and dichotomous dependent clinical variables, in advance, in individual patients with septic shock and to integrate these into prospectively validated models. Two hundred forty (240) patients with septic shock who were entered into the placebo arm of a multi-institutional clinical trial were randomly separated into a model building training cohort (n = 154) and a predictive cohort (n = 86), which was used to prospectively validate the prognostic models built upon the training cohort database. From baseline patient demographics; hospital laboratory tests; and plasma levels of interleukin-6, interleukin-8, and granulocyte colony stimulating factor, multiple regression models were developed that predicted clinically important continuous dependent variables quantitatively in individual patients. Multivariate stepwise logistic regression was utilized to develop models that prognosticated dichotomous dependent end points. At the completion of the modeling process, baseline data from individual patients in the predictive cohort was inserted into each multivariate model for each day. Prospective validation was accomplished by simple linear regression of individual predicted versus observed values for continuous dependent variables, and by establishing the Receiver Operator Characteristics Area Under the Curve (ROC AUC) for logistic regression models that predicted dichotomous end points. Through seven days, SMART quantitative predictions of selected physiologic and metabolic parameters were validated at r > 0.500 in 51%. Up to seven days after baseline, 31/49 (63%) SMART models for renal and liver function indicators were validated prospectively at the r > 0.700 level. For hematologic/coagulation models, 37/56 (66%) up to seven days had r > 0.900. Among dichotomous models, ROC AUC > 0.700 was achieved in 30/49 (61%) during the first week. SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with septic shock.
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PMID:Prospectively validated prediction of organ failure and hypotension in patients with septic shock: the Systemic Mediator Associated Response Test (SMART). 1094 50

In vitro models of macrophage growth, differentiation, and function are needed to facilitate the study of their biology as important immune facilitator cells and as frequent targets of bacterial and viral infection. A simple method for the selective expansion and continuous culture of mouse macrophages from primary explant cultures of mouse embryonic tissue is described. Culture in Dulbecco modified Eagle medium (DMEM) low-glucose (1 g/L) formulation (DMEM/L) inhibited fibroblast growth. In contrast, macrophages continued to proliferate in the presence of DMEM/L when in contact with the fibroblasts. Alternating growth in high-glucose DMEM with DMEM/L produced a 1.16- to 2.1-fold increase (depending on mouse strain) in the percentage of macrophages within the cell culture in comparison with culturing in DMEM with high glucose exclusively. Macrophage yields of over 1 million cells/T12.5 flask were achieved by passages 3-4, and, thereafter, declined over the next 5-10 passages. The peak percentage of macrophages within a culture varied depending on the strain of mouse (C57BL/6, CD-1, and CF-1 and two knockout C57BL/6 strains deficient in either interleukin-6 [IL-6] or granulocyte colony stimulating factor [GCSF]). The GCSF (-/-)-derived cultures had the lowest peak macrophage content (30%) and CD-1 the highest content (64.9%). The IL-6 (-/-) and CD-1 cultures appeared to spontaneously transform to create cell lines (IL6MAC and CD1MAC, respectively) that were composed of 50-75% macrophages. The macrophages were phagocytic and were positive for CD14, acetylated low-density lipoprotein receptors, and F4-80 antigen. Light and electron microscopy showed that the cultured macrophages had in vivo-like morphological features, and they could be plated to high purity by differential attachment to petri dishes in serum-free medium.
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PMID:Macrophage population dynamics within fetal mouse fibroblast cultures derived from C57BL/6, CD-1, CF-1 mice and interleukin-6 and granulocyte colony stimulating factor knockout mice. 1563 2


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