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)

The constitutive production of interleukin-6 (IL-6), a potent hepatocyte-stimulating factor and B cell-differentiating factor, was demonstrated in 3 patients with cardiac myxomas. Tumor cells from the only patient who presented with immunologic features produced 14-23-fold higher levels of IL-6 than those from the 2 patients who lacked such features. A significant serum IL-6 level (56 pg/ml), greater than that observed in patients with active rheumatoid arthritis, was also observed only in this patient, with a subsequent return to an undetectable level after surgical removal of the tumor. This was associated with a regression of the immunologic features. This same patient was observed to have an IL-6-dependent, proliferative polyclonal plasmacytosis of the bone marrow. These observations demonstrate that an overproduction of IL-6 by cardiac myxoma cells, in association with a systemic passage of this IL-6, may be responsible for the immunologic features similar to those observed in true autoimmune diseases such as rheumatoid arthritis.
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PMID:Constitutive production of interleukin-6 and immunologic features in cardiac myxomas. 169 May 43

Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. It has been implicated in the control of connective tissue cells in such conditions as rheumatoid arthritis and osteoporosis. We have investigated the effects of recombinant human interleukin-6 (rhIL-6) on human osteoblastlike cells derived from explants of trabecular bone. ROS 17/2.8 cells were used as an additional osteoblastlike cell model system. We were unable to identify any effects of rhIL-6 (5-5000 pg/ml) on the proliferation, alkaline phosphatase activity. osteocalcin production, or release of cytokines or prostaglandins by either osteoblastlike cell model system. Since we have shown previously that these cells release IL-6 in culture, we used a sheep anti-human IL-6 antibody to investigate the possibility that (1) action of added exogenous IL-6 could be masking endogenous production, and (2) endogenous IL-6 may regulate the effects of osteotropic agents on the osteoblastlike cells. Presence of the antibody exerted no detectable effects on 1,25-(OH)2D3-stimulated alkaline phosphatase or on proliferation or TNF production enhanced by IL-1. Thus IL-6 does not appear to be involved in the regulation of osteoblast activity.
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PMID:Human osteoblastlike cells do not respond to interleukin-6. 170 32

Interleukin-6 (IL-6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL-6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P less than 0.001). The IL-6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r = 0.65; P less than 0.001), those of plasma. Furthermore, synovial fluid IL-6 concentrations in bilaterally inflamed knees were significantly correlated (r = 0.79; P less than 0.001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r = 0.75; P less than 0.001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL-6 and plasma C-reactive protein (CRP) concentration, and no correlation between IL-6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL-6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r = 0.72-0.94; P less than 0.005). These relationships suggest that IL-6 production in inflammed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease-related factors.
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PMID:Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients. 175 86

Cytokines and growth factors are important mediators of inflammation and play a major role in both the physiological regulation of bone and cartilage metabolism, and in the destruction of joint-related structures. These complex biological regulatory events have to be regarded as net effects which are dependent on the individual actions of the different cytokines and their corresponding inhibitors in the pericellular environment of the cells present in the inflamed tissues. These effects can be antagonized on various levels by natural or artificial inhibitory molecules. The determination and characterization of cytokines and their inhibitors in body fluids and tissues may contribute to a better understanding of the basic mechanisms of the pathogenesis of inflammatory joint diseases, and may help to develop better modalities of therapy. The objective of the present review is to outline important actions of selected cytokines and growth factors on cells and the surrounding matrix of bone and cartilage in rheumatoid arthritis. It will focus on interleukin-1 (IL-1), IL-1 inhibitors, Tumor-Necrosis-Factor-alpha (TNF-alpha), TNF inhibitors, Interleukin-6 (IL-6), colony-stimulating factors (CSF's), Interferon-gamma (IFN-gamma), growth factors, eicosanoids and prostaglandins, all of which are important in the effector phase of tissue destruction.
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PMID:[The role of cytokines and growth factors in rheumatoid joint destruction]. 179 55

Serum levels of phospholipase A2 (PLA2) activity have been shown to be elevated in cases of septic shock and rheumatoid arthritis. The cellular origin of serum PLA2, however, is not known. In this report, we demonstrate that human group II PLA2 expression and secretion are induced in hepatoma cells (HepG2) following treatment with interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1 (IL-1). Of the three cytokines, IL-6 is the most potent. Significant synergy is observed between IL-6 and IL-1 and between IL-6 and TNF, but not between IL-1 and TNF. PLA2 induction does not occur in human YT cells, which are known to have receptors for both IL-1 and IL-6, indicating that the regulatory mechanism involved is cell type-specific. The results of RNA blot analysis indicate that the PLA2 gene is regulated in HepG2 cells at the pretranslational level. Induction of PLA2 synthesis in HepG2 cells in response to these cytokines resembles the induction of the acute phase plasma proteins which are synthesized in cultured hepatocytes and hepatoma cells following exposure to the same cytokines and in liver in response to inflammation and infection. In addition, a putative IL-6-responsive element, which is homologous to a similar element found in several acute phase genes, is present in the 5'-promoter-proximal region of the PLA2 gene. These results suggest that serum PLA2 is synthesized in and secreted from liver cells in response to inflammatory stimuli, mediated primarily by IL-6, and therefore should be classified as an acute phase protein.
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PMID:Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. 184 31

We present a double-antibody radioimmunoassay for determining human interleukin-6 (IL-6) in biological fluids. The detection limit of the assay is 20 ng/L (B0 - 2 SD). Bound radioactivity in the range of 30% to 90% of the B0 counts corresponds to IL-6 concentrations of 100 to 14,000 ng/L. Analytical recovery of IL-6 added to EDTA-treated plasma averaged 25% more than that added to serum. The plasma concentration of IL-6 was therefore approximately 85 ng/L more than the concentration in simultaneously drawn serum. The mean serum concentration of IL-6 in 45 healthy subjects was 83 ng/L (range 20-290 ng/L), in 20 patients with multiple myeloma 303 ng/L, in 20 patients with rheumatoid arthritis 234 ng/L, and in 13 patients with systemic lupus erythematosus 183 ng/L. Markedly increased (greater than 3000 ng/L) concentrations of IL-6 were found in sera of patients with meningococcus meningitis and infectious peritonitis.
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PMID:Radioimmunoassay of interleukin-6 in plasma. 191 67

A prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage.
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PMID:Urinary IL-6: a marker for mesangial proliferative glomerulonephritis? 191 27

Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP.
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PMID:[Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura]. 192 Aug 40

Synovial fluids (SF) and sera (S) from patients with rheumatoid arthritis (RA) were examined for IgM, IgM-rheumatoid factor (IgM-RF), albumin and interleukin-6 (IL-6) activity. The quotient of SF/S IgM-RF was elevated compared with that of SF/S albumin in 7 patients with seropositive RA, although the quotient of SF/S IgM was lower than that of SF/S albumin. SF IL-6 activity was much higher than serum IL-6 activity in all the 7 RA patients. In synovial fluids from 22 seropositive RA patients, SF IL-6 activity was significantly correlated with the SF IgM-RF, IgG-RF and IgA- less than RF, but not with SF IgM, IgG or IgA. Moreover, SF IgM-RF as well as SF IL-6 activity was significantly correlated with the Westergren erythrocyte sedimentation rate (ESR) or the Lansbury articular index. These results indicate that IL-6 and RF might be produced within the rheumatoid joints as a result of abnormal immune system activation, which is associated with the disease activity of RA. Three of the 4 seronegative RA patients, however, showed high SF IL-6 without detectable levels of SF IgM-RF, indicating that IL-6 alone is not sufficient for IgM-RF production.
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PMID:Correlation between rheumatoid factor and IL-6 activity in synovial fluids from patients with rheumatoid arthritis. 193 84

Polyclonal antibodies were raised in rabbits against Interleukin-6 (IL-6) by immunisation with a synthetic peptide of identical sequence to the amino terminal 12 amino acids of human IL-6. These antibodies reacted with recombinant IL-6 by ELISA and stained the cytoplasm of the IL-6 secreting bladder tumour cell line T24. Staining was abolished by prior incubation of the antibody with the IL-6 peptide. F(ab')2 fragments made by pepsin digestion of the IgG were immunopurified, labelled with biotin and retained activity in the biochemical and histological assays. Sections of synovial membrane from patients with rheumatoid arthritis (RA) were stained with these antibodies, using an immunoperoxidase technique, and cells containing IL-6 were domonstrated in the thickened synovial lining layer and also in a perivascular distribution in the deeper synovium. In osteoarthritis there were fewer cells in the lining layer and hence localisation appeared similar in both the interstitial area and lining layer. Double-staining techniques with mouse monoclonal antibodies against cell subset markers in five RA synovial membranes showed that up to 13% of T-cells and 19% of antibody-producing cells stained for IL-6. However, up to 70% of the macrophages contained IL-6 and these were found in close proximity to Ig-producing plasma cells. This study showed that macrophages were the major cells of the immune system in which IL-6 could be localised in RA, and suggests a role for locally produced IL-6 in the stimulation of rheumatoid factor production.
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PMID:Interleukin-6 localisation in the synovial membrane in rheumatoid arthritis. 194 69


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