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

Inbred animals (Lewis rats) were used to investigate the regeneration of autologously implanted splenic tissue at intra-omental and subcutaneous sites. Quantitative immunohistology with monoclonal antibodies against lymphocytes and macrophages was performed to analyse the cell density of red pulp (RP), periarteriolar lymphoid sheath (PALS), marginal zone (MZ) and follicle, 7-180 days after transplantation. Antigenic, allogeneic and mitogenic stimulation and Northern blotting were also performed. Transplant groups differed from spleen only in the reduced size of PALS; however, quantitative analysis demonstrated subtle differences between spleen and transplants. The cell density of B-cells and ED-1+ macrophages was reduced in the RP, Tsupp/cyt-cells were decreased and B-cells increased in PALS, and B-cells and Thelper-cells reduced in the MZ. No differences could be detected between the transplant groups. Flow-cytometric analysis of cell suspensions from spleen and transplants revealed a reduction of T-cells (OX-19+), MHC-I and transferrin-receptor-bearing cells in both transplant groups, and a decrease in the number of Thelper-cells and ED-3+ macrophages in subcutaneous transplants. Both transplant groups were defective regarding the allogeneic and pokeweed mitogen response. Aberration of the lipopolysaccharide response was restricted to subcutaneous transplants, which additionally showed abnormal expression of interferon-gamma, interleukin-5 and interleukin-6 mRNA. Thus, subtle alterations of the newly developed microenvironment and/or lymphocyte-homing may influence the regeneration of splenic tissue; the implantation site may represent an important parameter in functional reorganisation.
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PMID:Regeneration of autotransplanted splenic tissue at different implantation sites. 133 Mar 13

A human Epstein-Barr virus (EBV)-positive lymphoblastoid B cell line, named BA-D10-4, produces a factor of a molecular mass less than 10 kDa that promotes cell proliferation of both BA-D10-4 cells and other human T or B lymphoid cell lines, either EBV-positive or -negative. The factor synergizes with higher molecular mass autocrine growth factors and makes both BA-D10-4 cells and B cell lines from Burkitt's lymphoma, but not cells from T cell leukemia, more responsive to interleukin-1 and interleukin-6. Therefore, this low molecular mass factor seems to be an autocrine growth factor per se and to have the characteristics of a competence factor.
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PMID:Epstein-Barr virus-transformed B lymphocytes produce low molecular mass molecules with autocrine growth factor and competence factor activity. 133 48

The proto-oncoprotein c-Rel is a member of the nuclear factor kappa B transcription factor family, which includes the p50 and p65 subunits of nuclear factor kappa B. We show here that c-Rel binds to kappa B sites as homodimers as well as heterodimers with p50. These homodimers and heterodimers show distinct DNA-binding specificities and affinities for various kappa B motifs. In particular, the c-Rel homodimer has a high affinity for interleukin-6 (IL-6) and beta interferon kappa B sites. In spite of its association with p50 in vitro, however, we found a lymphoid cell-specific nuclear factor in vivo that contains c-Rel but not p50 epitopes; this factor, termed IL-6 kappa B binding factor II, appears to contain the c-Rel homodimer and preferentially recognizes several IL-6 kappa B-related kappa B motifs. Although it has been previously shown that the IL-6 kappa B motif functions as a potent IL-1/tumor necrosis factor-responsive element in nonlymphoid cells, its activity was found to be repressed in lymphoid cells such as a Jurkat T-cell line. We also present evidence that IL-6 kappa B binding factor II functions as a repressor specific for IL-6 kappa B-related kappa B motifs in lymphoid cells.
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PMID:A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 kappa B-related motifs whose activities are repressed in lymphoid cells. 137 88

Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety of cells, regulating immune response, acute phase reaction and hematopoiesis. In accordance with its pleiotropic functions, IL-6 is indicated to be involved in the pathogenesis of several diseases including autoimmunities, lymphoid malignancies and inflammations. An elevated level of IL-6 is demonstrated in patients with rheumatoid arthritis and cardiac myxoma, which can explain symptoms of these diseases, such as autoantibody production and increase in acute phase proteins. Therefore, inhibitors of IL-6 production or IL-6 receptor-mediated signal transduction may be used for treatment of IL-6-related diseases. The IL-6 receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R) and a non-ligand-binding signal transducer, gp130, both of which belong to the cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL-6R and gp130, and gp130 in turn transduces the signal. A nuclear factor for controlling IL-6 gene expression (NF-IL6) is also involved in the transcriptional regulation of various acute-phase protein genes. IL-6-stimulation of hepatocytes, through modification of pre-existing NF-IL6 protein, leads to binding of NF-IL6 to IL-6-responsive elements and activation of acute-phase protein genes. NF-IL6 is shown to recognize the enhancer core sequence of several viruses, suggesting a possible relationship of virus infection and IL-6 expression.
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PMID:Interleukin-6 and its receptor in autoimmunity. 138 Feb 41

Interleukin-6 (IL-6) is a pleiotropic cytokine and has been shown to support the growth of T and B lymphocytes in the presence of mitogens in vitro. IL-6 can induce human natural killer (NK) and interleukin-2 (IL-2)-induced lymphokine-activated killer cell (LAK) activity in vitro. It can also mediate antitumor effects in various murine models. In order to understand the mechanism of in vivo action, we have investigated the proliferation of lymphoid cells in vivo and the effects on NK, and LAK cell activities in response to IL-6 administration in mice. In vivo proliferation was measured by labeling the DNA of dividing cells with [125I]iodo-2'-deoxyuridine. C57BL/6 mice were injected ip with either IL-6 or HBSS control two times a day for 3 days and in vivo proliferation was measured. For comparative purpose IL-2 was administered and in vivo effects were analyzed. IL-6 caused significant proliferation of cells mainly in the spleen, while, IL-2 caused proliferation in the lungs, liver, spleen, and kidneys. Pretreatment irradiation (500 rad) of mice abrogated the IL-6-induced proliferation indicating radiosensitive cells are involved. Furthermore, in vivo proliferation was not observed in young nude mice treated with IL-6. To investigate whether the proliferating cells were cytotoxic, we tested for LAK (vs. fresh MCA-102 tumor targets) and NK (vs. Yac-1 tumor targets) activities in the organs of mice treated with IL-6 or IL-2 by 4 h 51Cr-release assay. IL-2 administration induced the generation of LAK activity and increased NK cytotoxicity in various organs, but IL-6 had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic administration of recombinant interleukin-6 in mice induces proliferation of lymphoid cells in vivo. 139 Dec 32

A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki-67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi]-negative), different from that of normal plasma cells (IL-6-negative/GST-pi-positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non-Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL.
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PMID:Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas. 141 84

Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.
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PMID:Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes. 151 71

Oncostatin M, a cytokine produced by activated lymphoid cells, regulates the growth and differentiation of a number of tumor and normal cells. In contrast to its effects on normal endothelial and aortic smooth muscle cell cultures, Oncostatin M was a potent mitogen for cells derived from acquired immunodeficiency syndrome-related Kaposi's sarcoma (AIDS-KS). After exposure to Oncostatin M, AIDS-KS cells assumed a spindle morphology, had an increased ability to proliferate in soft agar, and secreted increased amounts of interleukin-6. Oncostatin M RNA and immunoreactive Oncostatin M protein were found in AIDS-KS-derived cell isolates. These results suggest that Oncostatin M may play a role in the pathogenesis of AIDS-KS.
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PMID:Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. 154 93

Among several rat hepatoma cell lines known to secrete interleukin 6 (IL6), the HTC.JZ1 line stands out as a high-level producer. HTC.JZ1 cells were stimulated to secrete up to fourfold increased amounts of IL6 over 24 hours by treatment with lipopolysaccharides (LPS). Both functional IL6 levels, measured as hepatocyte stimulating factor (HSF) activity, and IL6 mRNA concentrations were increased proportionally by exposure to LPS. Similarly, IL6 mRNA was induced by LPS treatment in cultured primary rat hepatocytes. The induction of Il6 mRNA by LPS was inhibited both in primary hepatocyte and hepatoma cell cultures by treatment with the synthetic glucocorticoid dexamethasone, consistent with the known analogous repression of the IL6 gene by dexamethasone in macrophages, monocytes and fibroblasts. IL6 secreted by HTC.JZ1 cells was utilized as an autocrine inducer of endogenous acute phase gene expression: HTC cells expressed constitutive levels of alpha 2-macroglobulin (alpha 2M) mRNA specified by the major rat acute phase gene, the alpha 2M gene, which is known to be regulated by IL6. By contrast, normal rat liver biopsy material and a number of other rat hepatoma cell lines lacked endogenous IL6 production and showed very low to zero expression of endogenous alpha 2M mRNA. Expression of alpha 2M mRNA in HTC.JZ1 cells was inducible by treatment with LPS. The constitutive and the LPS-induced production of alpha 2M mRNA were significantly reduced (up to 50% inhibition) by addition of an anti IL6 serum to the culture medium and removal of the immune complexes. However, complete neutralization of the alpha 2M-inducing HSF activity could not be obtained with anti-IL6 serum alone, probably because HTC.JZ1 cells secrete comparable quantities of a second HSF activity. This activity, the cytokine leukemia inhibitory factor (LIF), is also known to stimulate transcription of the rat alpha 2M gene but was not reactive with anti-IL6 sera. The induction of IL6 mRNA in HTC cells by LPS was regulated at the transcriptional level, as demonstrated by a series of mutagenesis and transfection experiments. Progressive deletion of 5' flanking sequences from the IL6 gene promoter region reduced the basal level, and the LPS-induced promoter activity after transfection into HTC.JZ1 hepatoma cells. IL6 has been shown to act as an autocrine regulator of growth for certain B lymphoid cell lines derived from human multiple myelomas. The results presented here establish that IL6 secreted by certain hepatoma cell lines also acts in an autocrine fashion to induce expression of the endogenous acute phase alpha 2M gene.
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PMID:Autocrine activity of interleukin 6 secreted by hepatocarcinoma cell lines. 171 34

Clinical trials to evaluate the potential of adoptive immunotherapy in cancer patients have been restricted to the use of lymphoid effector cells. Of the other probably even more important host defense system against tumor growth, the mono-nuclear phagocyte system, only monocytes (mo) have been reinfused which, however, represent immature precursor cells and acquire full functional competence only upon further maturation. This is a report on 7 patients who received autologous macrophages (MO) grown in vitro from blood mo and activated by interferon-gamma (IFN gamma). Mononuclear cells were isolated from whole blood by cytapheresis and cultured for 7 days with 2% autologous serum on hydrophobic Teflon foils. Eighteen house before cell harvest, recombinant human IFN gamma was added at 200 IU/ml. Mo-derived MO were purified by counter-current elutriation. Starting with 10(8) MO cells, therapy was escalated up to the maximal number of MO obtainable from one single preparation cycle. Currently, 26 therapies have been performed with the maximal dose being 1.7 x 10(9) MO per infusion. Except for low grade fever (less than 38 degrees C), MO autografts were well tolerated, with no side effects observed. Biological response was followed by analyzing the serum levels of beta 2-microglobulin, neopterin, interleukin-6, tumor necrosis factor, and lysozyme. While in 3 out of 7 patients serum neopterin increased in response to MO therapy, other biological response parameters remained at pretreatment levels. Radiolabeled MO were shown to first accumulate in the lungs, then to pool into liver and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new approach to adoptive immunotherapy of cancer using tumorcytotoxic macrophages grown from peripheral blood monocytes. 175 53


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