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)

I propose that central nervous system endothelial cells are directly or indirectly responsible for the brain pathology in hepatic encephalopathy, and that this damage to the central nervous system is mediated by specific cytokines and nitric oxide which activate endothelial cells and thereby alter their cell functions. Liver diseases are conditions characterized by high circulating levels of cytokines, namely interleukin-1, interleukin-6 and tumor necrosis factor. Interactions between these cytokines and central nervous system endothelial cells may trigger a cascade of events including enhanced blood-brain barrier permeability, brain edema, astrocyte alterations and gliosis. Cytokine-induced production of nitrogen reactive molecules by endothelial cells themselves may also lead to further cellular damage and neuronal dysfunction. This hypothesis may explain several characteristics of hepatic encephalopathy including reversibility, disease progression and clinical features. It also suggests potential ways of intervention.
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PMID:The role of central nervous system endothelial cell activation in the pathogenesis of hepatic encephalopathy. 867 59

We have examined the effects of irradiation on the cytokine secretion from genetically modified human esophageal and gastric carcinomas. Both cell lines were transduced retrovirally to secrete interleukin-2, interleukin-6 and granulocyte-macrophage colony-stimulating factor, respectively. The metabolism of all the transduced cells was partially inhibited by 6 Gy, and greatly inhibited by 20 Gy irradiation. Cytokine productions, however, was not affected by 6 Gy in many cases, and continued to be detected even after 60 Gy irradiation. The analysis of the dose and time of irradiation in each cytokine producer is useful for the designing of tumor vaccine using cytokine gene transfer.
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PMID:Study of irradiation effects on cytokine secretion from retrovirally-transduced tumor cells: a model for tumor vaccination. 868 10

Induction of hepatic nitric oxide synthase (NOS) by tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), interleukin-6 (IL-6), and lipopolysaccharide was assessed as activity and immunoreactive protein. Hepatic NOS activity was cytosolic and had cofactor requirements consistent with inducible nitric oxide synthase (NOS2). NOS induction by TNF alpha was dose dependent from concentrations of 0.06 to 60 nM and was increased 2-3-fold by IFN gamma. NOS induction was reflective of total TNF alpha binding to hepatocyte receptors. Hepatocyte TNF alpha binding fit a biphasic curve with high affinity (K(d) = 1.4 nM, Bmax = 3157 sites) and low affinity (K(d) = 157 nM, Bmax = 204,948 sites) elements. NOS2 activity was induced by lipopolysaccharide, IL-1 beta, TNF alpha, and IFN gamma but not by IL-6. All cytokine stimuli were inhibited by antioxidants. Oxygen radical generation was directly measured as dichlorofluoroscein fluorescence in isolated mitochondria. Mitochondria from TNF alpha-treated hepatocytes generated more oxygen radicals than did controls. Antioxidants reduced mitochondrial generation of oxygen radicals. Activation of the transcription factor nuclear factor-kappa B by TNF alpha, IFN gamma, and IL-1 beta was assessed by gel shift analysis. Cytokine treatment increased nuclear factor-kappa B binding, and the addition of antioxidants or rotenone inhibited cytokine activation. Taken together, these data suggest that oxygen radicals, possibly generated by mitochondria, play a major role in NOS2 induction by cytokines.
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PMID:Characterization of hepatic nitric oxide synthase: identification as the cytokine-inducible form primarily regulated by oxidants. 870 Jan 34

The immune system is a complex network that regulates and maintains the host's defense system. Changes and alterations in the immune system precipitate a series of reactions to prevent further damage as well as initiate repair. The system's cellular component relies on cytokines (interleukins, tumor necrosis factor, interferons, etc.) to facilitate communication in response to a foreign antigen. Cytokine concentrations are therefore elevated during times of inflammation, such as rejection of a transplanted organ. Recent research suggests that interleukin-6 may have an inhibitory effect on cytochrome P-450 3A and thus affect drug metabolism. Cyclosporine, which is administered to prevent rejection of transplanted organs, is metabolized primarily by the P-450 3A system. Thus, the inhibitory effect of interleukin-6 may alter cyclosporine concentrations, which in turn may increase its adverse effects, such as nephrotoxicity.
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PMID:Drug-cytokine interactions: focus on cyclosporine. 872 98

Interleukin-6 (IL-6) and the complement activation products C3bc and terminal complement complex (TCC) were measured in three groups of children undergoing open heart surgery. One group was treated with intraoperative extracorporeal ultrafiltration and postoperative autotransfusion of shed mediastinal blood, one group was subjected to autotransfusion only and in one group none of these procedures were performed. No differences between the groups were observed concerning the degree of complement activation. Peak and total accumulated level of IL-6 was significantly higher in the group subjected to ultrafiltration and autotransfusion compared to the group treated conventionally with no interventions. IL-6 may be a sensitive marker of maneuvres increasing the inflammatory load during and after open heart surgery in children.
Cytokine 1996 May
PMID:Release of interleukin 6 and activation of complement during and after paediatric cardiopulmonary bypass. Effect of autotransfusion of shed mediastinal blood and ultrafiltration. 872 71

In patients with childhood sickle cell disease (SCD) serum interleukin-6 (IL-6) levels were measured during the steady (healthy) state of disease. The corresponding measurements were made in comparable healthy normal controls. Serum IL-6 levels were assessed via ELISA in 27 SCD patients and 19 controls. Results revealed significantly higher circulating levels of IL-6 in the SCD patients (60 +/- 7 pg/ml) compared with the healthy controls (12 +/- 5 pg/ml). IL-6 is a multifunctional cytokine that plays a central role in host defense mechanisms. The impact of high circulating levels of IL-6 may be deleterious to humoral and cell-mediated immune functions in SCD, with resultant heightened risk for morbidity.
J Interferon Cytokine Res 1995 Dec
PMID:Serum interleukin-6 levels in the steady state of sickle cell disease. 874 87

Treatment of the cell wall of Candida albicans with ethylenediamine yields an extract that is antigenic for both the humoral and cell-mediated arms of the immune system. This extract has been shown in previous studies by this laboratory and others to possess potent immunomodulatory activity. We report results here that show that treatment of the macrophage-like cell line RAW 264.7 with the ethylenediamine cell wall (EDA-CW) extract results in an increase in the production of both interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Our results also show that the EDA-CW extract possess potent costimulatory activity when combined with interferon-gamma (IFN-gamma). We have found, on the other hand, that EDA-CW extract-treated cells fail to produce elevated levels of IL-1 either alone or in combination with IFN-gamma as a costimulus. Our analysis also shows that the activation of TNF-alpha production by the EDA-CW extract appears to be at the level of transcription, since Northern blot analysis shows that the increase in the level of TNF-alpha mRNA is essentially identical to the rise in TNF-alpha activity released. We suggest that a component of the immunomodulatory activity of the EDA-CW extract is via the activation of macrophage function.
J Interferon Cytokine Res 1996 Jun
PMID:Production of IL-6 and TNF-alpha by the macrophage-like cell line RAW 264.7 after treatment with a cell wall extract of Candida albicans. 880 1

Cardiotrophin-1 (CT-1) is a new member of the interleukin-6 cytokine family that was identified from a mouse embryoid body cDNA library by expression cloning. Mouse CT-1 induces features of hypertrophy in neonatal rat cardiac myocytes and binds to and activates the leukaemia inhibitory factor/gp130 receptor complex. In this work we report the isolation and characterization of cDNA and genomic clones encoding human CT-1. These clones encode a 201 amino acid protein that is 80% identical to the mouse protein. Human CT-1 produced by transfection of the cDNA clones into mammalian cells induces the hypertrophy of neonatal rat cardiac myocytes. Human and mouse CT-1 bind to the leukaemia inhibitory factor receptor on both human and mouse cell lines indicating a lack of species specificity. No binding to the human oncostatin M specific receptor was detected. A 1.7 kb CT-1 mRNA is expressed in adult human heart, skeletal muscle, ovary, colon, prostate and testis and in fetal kidney and lung. The coding region of CT-1 is contained on three exons and is located on human chromosome 16p11.1-16p11.2.
Cytokine 1996 Mar
PMID:Human cardiotrophin-1: protein and gene structure, biological and binding activities, and chromosomal localization. 883 32

The pleiotropic cytokine interleukin-6 (IL-6) has been predicted to be a protein with four antiparallel alpha-helices. On target cells, IL-6 interacts with a specific ligand binding receptor subunit (IL-6R), and this complex associates with the signal-transducing subunit gp130. Human IL-6 acts on human and murine cells, whereas murine IL-6 is only active on murine cells. The construction of chimeric human/murine IL-6 proteins has allowed us to define a region (residues 77-95, region 2c) within the human IL-6 protein that is important for IL-6R binding and a region (residues 50-55, region 2a2) that is important for IL-6R dependent gp130 interaction. Guided by sequence alignment and molecular modeling, we have constructed several IL-6 variants with point mutations in these regions and have tested them for receptor binding and signal initiation. Within region 2c, phenylalanine 78 was involved in receptor binding, whereas lysine 54 within region 2a2 participated in gp130 activation. Furthermore, some IL-6 variants with lysine 54 replacements could be used to construct muteins that retained receptor binding but failed to activate gp130. Such IL-6 muteins were efficient IL-6 receptor antagonists.
J Interferon Cytokine Res 1996 Aug
PMID:Identification of single amino acid residues of human IL-6 involved in receptor binding and signal initiation. 887 26

Cardiac myxomas, the most common primary heart tumors in adults, show a variety of clinical manifestations and laboratory findings correlated with elevated interleukin-6 (IL-6) serum concentration. The aim of this study was to determine the expression of IL-6 mRNA in myxoma tissue as a cause to frequent immunologic abnormalities in patients with such tumors. In our centers, we analyzed 17 surgically resected myxomas using the polymerase chain reaction (PCR) and found increased IL-6 mRNA expression in 14 of 17 cases. The serum IL-6 levels of the 14 patients, detected by enzyme-linked immunosorbent assay (ELISA) with mouse antihuman monoclonal antibody (mAb), were high preoperatively (> 6 pg/ml) and decreased to normal postoperatively (< or = 6 pg/ml). These same 14 patients exhibited significant autoimmune disorders preoperatively. The other 3 patients had normal serum levels of IL-6 (< or = 6 pg/ml) and did not present any serious signs and symptoms, and molecular analysis did not show overexpression of IL-6 mRNA in neoplasmic tissue. These results suggest that IL-6 is overproduced in myxoma tissue and secreted into the systemic circulation as a stimulator of the immunoregulatory system. Furthermore, this study indicates the promising role of molecular biology techniques in the research of pathophysiologic mechanisms of cardiac myxomas.
J Interferon Cytokine Res 1996 Aug
PMID:Correlation of interleukin-6 gene expression to immunologic features in patients with cardiac myxomas. 887 29


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