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

Individual interferon-gamma (IFN-gamma) producing cells in activated human peripheral blood mononuclear cells (PBMC) were characterized by in situ hybridization using [35S]-labelled antisense RNA probes. The proportion of positive cells expressing IFN-gamma mRNA varied according to the substances used for stimulation. IFN-gamma mRNA expressed a relatively low percentage of 1-8% PBMC after a single stimulus with mitogens or OKT-3 antibody and 20-30% of the cells were identified to synthesize IFN-gamma mRNA after stimulation with PHA + P-MA + OKT-3 antibody. The expression of IFN-gamma mRNA and production of the lymphokine was dependent on accessory cells. If accessory cells were replaced by recombinant interleukin-1 (IL-1) plus interleukin-6 (IL-6), then T-cell proliferation to phytohaemagglutinin (PHA) could be partially restored and measurable amounts of IFN-gamma were detected. The addition of interleukin-2 (IL-2) or phorbol-12-myristate-13-acetate to T cells stimulated with PHA, IL-1 and IL-6 did not restore the production of IFN-gamma to an extent comparable to that produced by T cells stimulated in the presence of accessory cells. In further studies, depletion of T-cell subsets showed that CD3+, CD4+, CD8+, CD29+ and CD45RA+ cells were involved in IFN-gamma production after mitogenic stimulation. In conclusion, our data demonstrate that IFN-gamma production is dependent on signals from accessory cells and IFN-gamma is synthesized by only a small proportion of T cells, that did not belong to a unique population, characterized by conventional cellular surface antigens.
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PMID:In situ hybridization of interferon-gamma producing peripheral blood mononuclear cells. 190 64

Immunophenotype and functions of the malignant T cells to secrete various T-cell derived lymphokines and to respond in autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR) of the six patients with peripheral T-cell lymphomas (PTL) are presented. Three cases showed CD3/TcR alpha beta discordance (1 CD3+/TcR alpha beta-; 2 CD3-/TcR alpha beta+) and one showed absence of both these antigens (CD3-/TcR alpha beta-). In addition, we found that 50% of cases expressed CD25+, CD38+, and CD71+ activation antigens. The CD3/TcR alpha beta discordance and expressions of activation antigen noted in these cases were typical and similar to those reported from elsewhere. These malignant T cells from all cases whether CD25+ or CD25- (resting) expressed elevated interleukin-2 receptors (IL-2R) on stimulation with phytohemagglutinin (PHA) or human recombinant interleukin-2(rIL-2), and secreted elevated IL-2 by PHA, than do T cells from patients with tuberculosis (TB) or normal healthy controls. These malignant T cells also demonstrated elevated AMLR but deficient MLR B cells growth factor (BCGF) (except in one unusual case) secretion was increased, whereas B-cell differentiation factor (BCDF) secretion decreased. These results suggest that malignant T cells from lymph nodes of patients with PTL have uniform multiple immunologic defects in IL-2, BCGF, and BCDF lymphokine secretion and respond in AMLR and MLR, which do not correlate with immunophenotype or histologic types. These functions differentiate them from lymph-node T cells of patients with TB or blood T cells of normal healthy controls.
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PMID:Peripheral T-cell lymphomas. Immunophenotype, lymphokine production, and immunologic functional characteristics of the lymph-node malignant T cells. 195 33

Human Interleukin-6 (IL-6) is a cytokine secreted by T cells, as well as a variety of other cell types, which exhibits B-cell differentiating activity. The recent cloning of the gene that codes for this molecule has allowed us the opportunity to study the function of this molecule alone and in conjunction with other lymphokines in human B-cell isotype-regulation and differentiation. Recombinant human IL-6 enhances immunoglobulin (Ig) M and G secretion by B-cells activated by Staphylococcal A Cowan strain (SAC) and enhances IgM, IgG, and IgA secretion by B-cells activated by pokeweed mitogen. IL-6 also augments immunoglobulin secretion of differing isotypes from various Epstein-Barr Virus transformed B-cell lines. However, IL-6 does not alter the secreted isotype of naive surface IgM-positive B-cells. As human T-cells secrete other lymphokines in association with IL-6 after activation we examined the interaction of Interleukin-2 (IL-2) gamma-interferon (IFN-gamma) and Interleukin-4 (IL-4) with IL-6 on B-cell immunoglobulin secretion. IL-2 and IL-4 synergized with IL-6 in augmenting immunoglobulin secretion by SAC-activated B-cells. IFN-gamma significantly inhibited the Ig secretion of SAC-activated B-cells cocultured with IL-6 alone or in combination with IL-2. These results demonstrate that human recombinant IL-6 augments immunoglobulin secretion of isotype-committed B-cells but it does not induce a change in the isotype secreted. In addition, this lymphokine synergizes with IL-2 and IL-4 in supporting Ig secretion. However, IFN-gamma significantly inhibits IL-6 induced Ig secretion.
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PMID:The role of human interleukin-6 in B-cell isotype regulation and differentiation. 210 75

Stimulated human monocytes/macrophages are a source of interleukin-6 (IL-6), which is a likely mediator involved in immune and inflammatory reactions. The means to control production of IL-6 by these cells could therefore have therapeutic applications. We report here, for lipopolysaccharide (LPS)-stimulated human monocytes in vitro, that the lymphokine, interferon-gamma (IFN-gamma) (100 U/ml), enhanced the level of IL-6 activity, whereas another lymphokine, interleukin-4 (IL-4) (greater than or equal to 0.1 U/ml; greater than or equal to 1.2 x 10(-11) M), suppressed it. The effects of the two lymphokines were manifested at the level of mRNA. The action of the IL-4 was similar to that of the glucocorticoid, dexamethasone, but observed at a lower molar concentration. Such regulation of monocyte IL-6 activity is similar to that found previously for interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) synthesis.
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PMID:Contrasting effects of interferon-gamma and interleukin-4 on the interleukin-6 activity of stimulated human monocytes. 212 Jan 29

Administration of recombinant interleukin-6 (IL-6) was found to induce in vivo generation of cytotoxic T lymphocytes (CTL) against syngeneic transplantable erythroleukemia (FBL-3) in lymph node cells and peritoneal exudate cells (PEC) in C57BL/6 mice. Furthermore, 15 out of 16 C57BL/6 mice injected with 5 x 10(6) viable FBL-3 cells survived on day 100 when they were treated with 5 x 10(4) U of recombinant IL-6 three times a day on days 1, 2, 3, 5, 7 and 9 after the inoculation of tumor cells (the cure rate was 94%). Cured mice could reject the tumor cells rapidly after the re-inoculation of a large number of live FBL-3 cells. In contrast, all normal mice died of tumor development by day 10. In these cured mice, FBL-3-specific CD4-8+ CTL cells were found to be generated in PEC, spleen and lymph node cells by either in vivo or in vitro re-stimulation with FBL-3 cells, but lymphokine-activated killer cells never developed. The results suggested that the anti-tumor effect of IL-6 was mediated by in vivo induction of tumor-specific CTL.
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PMID:The in vivo anti-tumor effect of human recombinant interleukin-6. 212 76

Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-alpha despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-kappa B transcription factor-binding motifs and binds an IL-1-TNF-alpha-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular localizations of this factor are indistinguishable from those of NF-kappa B. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-alpha in vivo. These results indicate that a nuclear factor indistinguishable from NF-kappa B is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-alpha.
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PMID:Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines. 240 50

Human peripheral blood mononuclear cells develop a powerful lytic capacity when cultured in vitro with interleukin-2 (IL-2), becoming lymphokine-activated killer cells (LAK cells). As part of an investigation into means of influencing this process, the effect of other cytokines has been examined. In this study we describe the ability of interleukin-6 (IL-6) to regulate the induction and function of human LAK cells. The results show that substitution of IL-6 for IL-2 did not lead to the development of functional LAK cells, nor was IL-6 able to alter the lytic capacity of established LAK cells. However, when IL-6 was included with IL-2 during the induction phase of the LAK cells, the resulting cells displayed considerably greater lytic activity than those prepared with IL-2 alone. This effect was IL-6 dose-related. These results indicate that LAK cell development may be positively regulated in vitro; the implications of this observation for the clinical usage of LAK cells are discussed.
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PMID:Interleukin-6 enhances the induction of human lymphokine-activated killer cells. 240 52

The proliferation and differentiation of astrocytes are fundamental events in the normal development and function of the central nervous system (CNS), and may also contribute to the pathogenesis of a number of neurological diseases. Products of T lymphocytes can stimulate proliferation of astrocytes, but the nature of the T lymphocyte-derived molecule(s) responsible for this response is unknown. The present study was undertaken to examine several well-characterized T lymphocyte-derived factors for their ability to stimulate cultured primary rat astrocytes. While recombinant human interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and rat or human recombinant interferon-gamma (IFN-gamma) have no proliferative effect on astrocytes, a human T cell-derived B cell growth factor (BCGF) does. This BCGF, termed 2B11, had previously been characterized by its ability to enhance the proliferation of anti-mu-stimulated human B cells, while not influencing B cell immunoglobulin synthesis. High performance liquid chromatography (HPLC)-purified 2B11-BCGF (MW approximately 20,000 daltons) stimulates the proliferation of astrocytes in a dose-dependent fashion. Purified 2B11-BCGF also induced morphological differentiation and increased mRNA transcripts for glial fibrillary acidic protein (GFAP) in rat astrocytes. In addition to demonstrating the absence of effect of other known lymphokines, the effect on astrocytes attributed to 2B11-BCGF was confirmed by blocking its activity with a monoclonal antibody specific for 2B11-BCGF. Absorption experiments demonstrated that when BCGF activity was absorbed out by large, activated human B cells, astrocyte-stimulatory activity was also depleted. Rat astrocytes were able to partially absorb out both BCGF and astrocyte-stimulatory activity. These results suggest that 2B11-BCGF is responsible for stimulating astrocyte proliferation, and that human B cells and rat astrocytes may share a similar receptor for BCGF. These findings indicate that the growth and differentiation of astrocytes can be influenced by a T cell-derived lymphokine, 2B11-BCGF, whose activity thus far appears to be distinct from other reported cytokines.
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PMID:Human B cell growth factor enhances proliferation and glial fibrillary acidic protein gene expression in rat astrocytes. 248 87

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.
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PMID:Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia. 278 98

MHC nonrestricted cytotoxic cells play an important role in the killing of tumor cells in vitro and potentially in vivo. The activity of these cells is regulated by several cytokines such as IL-2 and IFN. In the present study we provide first evidence that IL-6 significantly augments the cytotoxic activity of human NK cells. IL-6 is produced by many different cells and is also known as IFN-beta 2, B cell stimulatory factor 2, hybridoma growth factor, hepatocyte-stimulating factor, and 26 kDa protein. IL-6 stimulates the activity of human CD3- NK cells but not that of CD3+ non-MHC-restricted cytotoxic T lymphocytes. As is the case with IL-2, the IL-6-mediated augmented cytotoxicity was a result of a more efficient lysis, but was not caused by an increased effector to target cell binding. Moreover, the effect of IL-6 on NK cell activity was blocked by a mAb directed against IL-2, and IL-6 itself was found to be a potent inducer of IL-2 production in cultured human PBMC. Thus it may be concluded that IL-6 enhances the cytotoxic activity of NK cells via IL-2. This newly recognized property of IL-6, which is produced by almost any cell, may be of importance in host defense against microbes and malignancies and therefore could contribute to improve the adoptive immunotherapy by using lymphokine-activated killer cells.
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PMID:IFN-beta 2/IL-6 augments the activity of human natural killer cells. 278 59


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