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

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.
Cancer Immunol Immunother 1990
PMID:Interleukin-6 enhances the induction of human lymphokine-activated killer cells. 240 52

Treatment of Daudi B-lymphoblastoid cells with low concentrations of either natural or recombinant human alpha-interferons inhibits cell proliferation and modulates the expression of a number of cell-surface antigens. Using a panel of monoclonal antibodies (MAbs) identifying determinants expressed at the surface of normal plasma cells, and polyclonal antibodies against surface and cytoplasmic immunoglobulin, we have found that growth inhibition is accompanied by plasmacytoid differentiation. Assays of growth stimulation of heterologous cells indicate that the culture medium from interferon-treated Daudi cells contains substantially more B-cell growth factor activity than that from control cells. However, the interferon-treated cells exhibit an impaired ability to respond to both these autocrine factors and exogenous factors produced by another Burkitt lymphoma line. These findings show that, in the case of Daudi cells, growth inhibition by interferons is closely associated with both terminal differentiation and a refractoriness to growth factors. In this system IFN-alpha may therefore be considered to be a B-cell differentiation factor, suggesting a possible basis for the anti-proliferative effects observed with certain human B-cell malignancies.
Int J Cancer 1987 Jul 15
PMID:Anti-proliferative effects of interferons on Daudi Burkitt lymphoma cells: induction of cell differentiation and loss of response to autocrine growth factors. 243 66

Tumour necrosis factor-alpha (TNF-alpha) is secreted by macrophages in response to inflammation, infection and cancer. Sublethal doses of recombinant TNF-alpha to rats causes cachexia, anaemia and inflammation. TNF-alpha plays a major part in tissue inflammation and remodelling by stimulating production of collagenase. Cellular responses to TNF-alpha are initiated by binding to high-affinity cell surface receptors. TNF-alpha then profoundly affects gene regulation, stimulating the fos, myc, interleukin-1 and interleukin-6 genes and inhibiting the type I collagen gene. Here we demonstrate that TNF-alpha also stimulates collagenase gene transcription; this stimulation is mediated by an element of the gene that is responsive to the transcription factor AP-1, the major component of which (jun/AP-1) is encoded by the jun gene; and that TNF-alpha stimulates prolonged activation of jun gene expression. This prolonged induction of jun contrasts with its transient activation by the phorbol ester TPA and provides a physiological example of the ability of jun/AP-1 to stimulate its own transcription. This may be a key mechanism for mediating at least some of the biological effects of TNF-alpha.
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PMID:Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. 253 68

Our study was designed to investigate the production of interleukin-1 (IL-1) and IL-6 in tumor-associated macrophages (TAM) isolated from ascites (18 cases) or solid (7 cases) human ovarian carcinoma. These are pleiotropic monokines which, in addition to affecting proliferation and differentiation of lymphocytes, act on various targets, including vascular cells and liver, and may therefore be involved in the pathogenesis of certain manifestations of malignancy. IL-1 was measured by the thymocyte co-stimulator assay, under conditions in which IL-6 was inactive, and, in 8 cases, by radioimmunoassay (RIA). IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line. TAM did not release appreciable levels of IL-1 spontaneously and, upon LPS stimulation, were poor producers of this monokine compared to blood monocytes. In contrast, TAM supernatants contained a high level of HGF in the absence of deliberate stimulation, and exposure to LPS either did not affect or further augmented production of this monokine. HGF activity of TAM supernatants was completely blocked by anti-IL-6 antibodies. Ascites fluid from 8 ovarian-carcinoma patients contained high levels of HGF activity, blocked by anti-IL-6 antibodies. Thus, TAM exhibit a dissociation in their capacity to release the functionally related monokines IL-1 and IL-6. IL-6 produced by TAM may account for the elevation of liver-derived acute-phase proteins associated with malignancy.
Int J Cancer 1989 Nov 15
PMID:IL-1 and IL-6 release by tumor-associated macrophages from human ovarian carcinoma. 258 59

A 13-year-old girl presented with general fatigue, back pain, anemia, hyperimmunoglobulinemia, and a mediastinal mass on chest radiograph. A mass was surgically removed, and its histologic examination determined the diagnosis of giant lymph node hyperplasia (Castleman's disease). With removal of the hyperplastic lymph node, the clinical symptoms soon disappeared and the abnormal laboratory findings were markedly improved within 1 month: serum IgG levels decreased from 4350 mg/dl to 1829 mg/dl. Immunostaining on the lymph node sections revealed polyclonal B-lymphocyte and T-lymphocyte populations. The patient's lymph node cells were cultured without any mitogenic stimulation, and the culture supernatants were assayed for their B-cell differentiation factor (BCDF) activity to induce IgG production by our Epstein-Barr virus-transformed cell line. The patient's lymph node cells produced high levels of BCDF activity: the supernatants could increase the IgG production from 140 ng/ml to 410 ng/ml when the values became from 140 ng/ml to 142 ng/ml or 148 ng/ml with those of the control lymph node cells. These results suggest that the hyperimmunoglobulinemia and its prompt improvement with removal of the hyperplastic lymph node may have been related to the spontaneous production of high levels of BCDF activity by the lymph node cells in the patient.
Cancer 1989 Jan 15
PMID:Giant lymph node hyperplasia (Castleman's disease) with spontaneous production of high levels of B-cell differentiation factor activity. 264 33

It has been demonstrated that interleukin-6 (IL-6) is a cytokine regulating immune response, acute-phase reaction and hematopoiesis. The deregulated expression of IL-6 was suggested to be actually involved in the pathogenesis of polyclonal B cell activation and autoimmune diseases such as rheumatoid arthritis. It could be hypothesized that continuous polyclonal B cell activation may be eventually leading to the generation of plasmacytoma/myeloma, possibly with additional expression of oncogene(s) such as c-myc gene. Therefore, future studies on the gene regulation of IL-6 would provide critical informations on the molecular pathogenesis of these diseases. Furthermore, IL-6 could be used as anti-cancer drug in certain tumors. Moreover, inhibitors of IL-6 such as anti-IL-6 monoclonal antibodies or soluble forms of IL-6 receptors could be useful in the treatment of such polyclonal/monoclonal B cell abnormalities.
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PMID:Interleukin-6: possible implications in human diseases. 266 8

The cytokine, interleukin-6 (IL-6), has emerged as a likely mediator of many of the systemic alterations observed in patients with cancer (fever, increased erythrocyte sedimentation rate, and alterations in plasma protein composition) and may also mediate local effects such as alteration in proliferation of tumor cells, increased tumor cell motility, and decreased intercellular adhesions between tumor cells. The distribution of IL-6 immunoreactivity in different human tumors was studied. IL-6 immunoreactivity was detected by the avidin-biotin-complex (ABC) procedure using a polyclonal rabbit antiserum raised against an E coli-derived human IL-6 (rIL-6). Preimmune rabbit serum used as a control did not yield specific staining and preadsorption of the IL-6 antiserum with rIL-6 abolished specific staining. Strong-to-moderate IL-6 immunoreactivity was observed in the neoplastic elements present in primary squamous cell carcinomas, in adenocarcinomas of mammary, colonic, ovarian, and endometrial origin, in various adenocarcinomas metastatic to lymph nodes, and in soft tissue tumors including leiomyosarcoma and neurofibrosarcoma. Weak-to-moderate IL-6 immunostaining was observed in Hodgkin's and non-Hodgkin's lymphomas. This study demonstrates that most human tumors stain positively for IL-6, adding weight to the hypothesis that IL-6 is a key cytokine that participates in the host-tumor interaction.
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PMID:Interleukin-6 immunoreactivity in human tumors. 267 20

Interleukin 6 (IL-6) was originally characterized as a B-cell differentiation factor, responsible for the terminal maturation of activated B cells to immunoglobulin producing cells. Recent works reveal that IL-6 has a wide variety of biological functions on various cells. In particular, IL-6 has been shown to augment the growth of freshly isolated human myeloma cells, and the myeloma cells constitutively produce IL-6 and express IL-6 receptors. Moreover, it has been shown that anti-IL-6 antibody can inhibit the in vitro growth of the myeloma cells. This is direct evidence that an autocrine loop is operating in freshly isolated myeloma cells, and that a constitutive production of IL-6 and activation of the IL-6 gene could be involved in the oncogenesis of human myeloma.
Cancer Surv 1989
PMID:Cytokines as autocrine growth factors in malignancies. 270 35

IL-6/IFN-beta 2 is a family of phosphoglycoproteins ranging in size from 19 to 30 kDa which elicits a broad range of physiologic and immune responses. Several cytokines, including TNF, have been shown to stimulate IL-6 production in cell culture. In this report, we describe the rapid induction of circulating biologically active IL-6 by the systemic administration of rTNF to patients with cancer. Low levels of IL-6 activity could be detected in the sera of patients as early as 5 min after rTNF infusion. IL-6 levels peaked approximately 2 to 3 h after rTNF bolus administration and were undetectable in most cases within 8 h. IL-6 was detected in two separate bioassays--the hybridoma B9 proliferation and the hepatocyte-stimulating factor assay. Maximum detectable levels of IL-6 ranged from 160 to 310 hybridoma growth factor units and 11-82 ng/ml in the hepatocyte-stimulating factor assay. IL-6 induction decreased after serial, daily doses of rTNF. Serial serum samples of patients receiving IL-2 or IFN-alpha were also assayed for IL-6 production. IL-2-treated but not IFN-alpha-treated patients generated low levels of IL-6 (range less than 20 to 95 hybridoma growth factor units/ml). Interestingly, in patients treated with IL-2, serum levels of TNF were detectable and peak TNF activity preceded measurable IL-6 levels. Serum levels of acute phase plasma proteins and of corticosteroid rose in response to rTNF administration. C-reactive protein increased (2.5 to 4.0-fold) within 8 h of rTNF administration and cortisol levels rose (10- to 20-fold) within 4 h after rTNF injection. We conclude that rTNF administration in man leads to the induction of circulating IL-6 which, due to its broad range of activities, may be an important physiologic signal regulating the immune response.
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PMID:IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. 278 45

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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