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)

We have previously shown that native human C-reactive protein (CRP) produces antitumor effects in experimental animals, and that these effects are mediated primarily through macrophages. More recently, we have observed that RS-83277, a synthetic peptide derived from CRP, appears to mimic the antitumor effects of native CRP. The purpose of this study was to determine the effects of RS-83277 on normal human monocyte and alveolar macrophage tumoricidal activity, and cytokine secretion. At optimal doses of 250-500 micrograms/ml, RS-83277 significantly enhanced tumoricidal activity of both monocytes and macrophages. RS-83287, a CRP peptide derived from a different site, had no effect at these doses. Specificity of RS-83277 for monocyte/macrophage-mediated cytotoxic activity was demonstrated by the failure of RS-83277 to enhance either natural killer (NK) or lymphokine-activated killer (LAK) cell-mediated activity. RS-83277 also augmented secretion of interleukin-1-beta (IL-1 beta) and interleukin-6 (IL-6) by monocytes. These data suggest a role for synthetic CRP peptide, RS-83277, as a novel biological response modifier in cancer therapy.
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PMID:Activation of human monocytes and alveolar macrophages by a synthetic peptide of C-reactive protein. 843 27

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin-6 (IL-6) which may display antitumor activity. Therefore, we evaluated sIL-6R levels in the sera of 15 patients who received cytokine-mediated immunotherapy with (IL-2/IFN-alpha), and 15 patients who received cell-mediated immunotherapy post-BMT, in an attempt to reduce the relapse rate. sIL-6R levels were evaluated pre-, during and post-cytokine or cell-mediated immunotherapy, using IL-6R-specific monoclonal antibodies (McAb) and double-sandwich ELISA. In normal controls, sIL-6R levels were found to be 20 +/- 3 ng/ml. sIL-6R levels increased significantly during IL-2/IFN-alpha immunotherapy in comparison to pre- or post-immunotherapy levels (74 +/- 9 ng/ml vs 46 +/- 6 ng/ml, and 50 +/- 9 ng/ml, respectively) (n = 15) (P < 0.05). sIL-6R levels also significantly increased following donor lymphokine activated killer (LAK) cells, given in addition to IL-2, in comparison to base line levels (87 +/- 3 ng/ml vs 60 +/- 2 ng/ml) (n = 6) (P < 0.05). Increased levels of sIL-6R were observed in BMT patients treated with immunotherapy.
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PMID:Soluble IL-6 receptors (sIL-6R) in hematological patients receiving immunotherapy with IL-2/IFN-alpha or donor lymphocytes following bone marrow transplantation. 889 86

This study examined the influence of a triathlon on the immune system and on serum amino acid concentrations. Eight male triathletes swam 2500 m, bicycled 81 km, and ran 19 km. The concentration of total serum amino acids decreased during the race, with the lowest values occurring 2 h postexercise. Similarly, serum glutamine concentration declined from 468 (SEM 24) (prerace) to 318 (SEM 20) mumol-1 (2 h postrace) and the natural killer (NK) and lymphokine activated killer (LAK) cell activities were suppressed 2 h postexercise (P < 0.05). Blood mononuclear cell proliferation decreased during exercise with the lowest value observed after running. The leucocyte concentration increased during and after exercise due to an increase in the concentration of neutrophils and monocytes. There was no significant change in lymphocyte concentration during or after the exercise. The plasma concentration of interleukin-6 did not change and the plasma concentration of interleukin-1 beta and tumor necrosis factor-alpha were below detection limits. The LAK cell cytotoxicity, but not NK cell activity or proliferative response, was significantly correlated with serum glutamine concentrations (r = 0.39, P < 0.01). This study confirms that prolonged endurance exercise results in changes in the cytotoxic function of the NK and LAK cells as well as the proliferative response. The time-course of changes in serum glutamine concentrations were best parallelled by changes in LAK cell activities.
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PMID:The immune system and serum glutamine during a triathlon. 895 90

In order to study adhesion-molecule expression and its consequences for cellular recognition, the presence of adhesion molecules ICAM-1, VCAM-1, VLA-4, LFA-1, alpha, LFA-1 beta, LFA-3, beta1-integrin and beta3-integrin was studied on specimens from breast tissue by immunohistochemistry and on cells from breast cell lines propagated in vitro. Breast-cancer tissue and the breast-cancer cell lines MCF-7, SK-BR-3 and ZR-75-1 showed expression of ICAM-1 and VLA-4 significantly lower than that of benign breast cells or normal breast epithelium. Of various cytokines tested, including recombinant human (rh) interleukin-6 (IL-6), rh tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), granulocyte/macrophage-colony-stimulating-factor (GM-CSF), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), only TNF was able to re-induce expression of ICAM-1 on cells from MCF-7, SK-BR-3 and ZR-75-1. Further, the ability of either unstimulated or lymphokine-stimulated killer (LAK) cells to recognize and lyse native or TNF-stimulated breast-cancer cells was studied. Whereas neither unstimulated lymphocytes or LAK cells were able to lyse untreated breast-cancer cells deficient for ICAM-1 expression, pre-treatment of tumor cells with TNF led to increased tumor-cell lysis. Anti-ICAM-1 antibodies, and pre-treatment of tumor cells with anti-TNF-receptor antibodies, abrogated these findings, corroborating their specificity. We thus conclude that the defective expression of ICAM-1 in our model might constitute a mechanism by which breast-cancer cells escape immunologic recognition and lysis by appropriate effector cells.
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PMID:Decreased expression of ICAM-1 and its induction by tumor necrosis factor on breast-cancer cells in vitro. 918 15

Benzydamine is a non-steroidal antiinflammatory drug, devoid of activity on arachidonic acid metabolism, which is extensively used as a topical drug in inflammatory conditions, particularly for the treatment of bacterial vaginosis and Candida albicans-sustained vaginitis. In the present study the effects of benzydamine on the production of several inflammatory cytokines were examined in cultures of Candida albicans-stimulated human mononuclear cells. Benzydamine (6.25-50 microM) inhibited Candida-induced tumor necrosis factor-alpha and, to a lesser extent, interleukin-1 beta production, whereas it did not affect interleukin-6 release. Benzydamine also blocked monocyte chemotactic protein-1 secretion, but it did not affect interleukin-8 production. Unlike benzydamine, ibuprofen and naproxen, two non-steroidal antiinflammatory drugs also used topically, were unable to suppress inflammatory lymphokine production from Candida-activated mononuclear cells. These data suggest that benzydamine may be effective in local Candida infections at least in part by suppressing inflammatory cytokine and monokine production in the vaginal mucosa and consequently decreasing their levels in vaginal secretions.
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PMID:Benzydamine inhibits the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1 by Candida albicans-stimulated human peripheral blood cells. 926 82

During infection and injury a series of metabolic events are activated that leads to a state of negative nitrogen balance and significant loss of lean body mass. This process is characterized by marked anorexia, net whole body protein breakdown, and liver anabolism. This host response initially is beneficial to the body because it helps it to fight disease and enhance healing. However, if such imbalance is maintained for long periods, it will invariably produce significant loss of lean body mass that may lead to a series of untoward clinical events. The role of the proximate cytokines, tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) as well as glucocorticoids as important mediators of many pathophysiological manifestations of infection and injury has been studied extensively. However, the involvement of other mediators, at least in skeletal muscle proteolysis during sepsis has been hypothesized, because blockade of glucocorticoids, TNF, IL-1, and IL-6 reduces but does not normalize protein breakdown rates nor does the direct application of these mediators to skeletal muscle in vitro enhance proteolysis. Furthermore other studies have suggested that the lymphokine, interferon-gamma (IFN-gamma, type II interferon or immune interferon), produces fever and enhances thermogenesis, body weight loss, and skeletal muscle depletion in rodents in a manner similar to that seen with TNF and IL-1. Cytokines appear to be major components of the host metabolic response during infection and injury. However, neither all the cytokines involved nor the exact mechanisms underlying their metabolic effects are completely understood. The regulation of muscle protein synthesis and breakdown, which largely determines the development of cachexia, appears to depend on the delicate balance between a number of regulatory substances including cytokines, glucocorticoids, catecholamines, insulin, and insulin-like growth factors.
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PMID:The role of cytokines in the catabolic consequences of infection and injury. 1008 3

Expression of the lymphokine genes in human astroglial cell lineages was studied. Primers for 7 different human lymphokines, from interleukin-1a (IL-1a) to interleukin-6 (IL-6), were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and 9 brain specimens by polymerase chain reaction (PCR). Two out of 5 unstimulated astrocytomas, U138MG and U373MG, expressed IL-6 genes. After stimulation with IL1beta, all astrocytoma and one neuroblastoma cell lines expressed IL-6 genes, but other leukemic cell lines did not show RNA transcripts of IL-6. In addition to the cultured cells, we examined IL-6 gene expression within human malignant astrocytoma, peritumoural brain and autopsied normal brains. The result shows that tumour and cells of the surrounding reactive lesion express IL-6 genes, but it is not expressed in normal brains. Next, the concentration of IL-6 in the supernatant of cultured cells was measured quantitatively by sandwich immunoassay, ELISA. IL-6 activity was present, but low in all astrocytomas with the exception of A172. Furthermore, the concentration of IL-6 increased markedly with the stimulation of IL-1beta in both a time- and dose-dependent fashion. A172 could also produce IL-6 as was seen in gene expression. From these results, it is suspected that astroglial cell-derived IL-6 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system.
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PMID:Expression of interleukin-6 gene in human astrocyte cell lineages. 1863 27

Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the TH17 subset of helper T cells and promoted angiogenesis. Interestingly, the 'angio-lymphokine' PlGF, in turn, specifically induced the differentiation of pathogenic TH17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with TH17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, TH17 cell development and autoimmunity.
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PMID:Placental growth factor regulates the generation of TH17 cells to link angiogenesis with autoimmunity. 3146 30


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