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 established a new cell line (TC-1) from primary site of a renal cell carcinoma (RCC) patient. Its doubling time in tissue culture was 20 hours at 45th passage and mycoplasma contamination test was negative. The karyotypic analysis demonstrated a human karyotype with a modal number of 70. A consistent chromosomal abnormality was noted such as No. 4 monosomy, No. 7 trisomy and a loss of Y chromosome. Electron microscopic examination showed a brush border, vacuoles and abundant glycogen granules in the cytoplasm, which was compatible with RCC cells. This cell line was transplantable to nude mice and the grown tumor closely resembled the original tumor, i.e. clear cell type and hypervascularity. High titer of interleukin-6 (IL-6) was detected in the supernatant of TC-1 cell culture (approximately 5 ng/ml) as well as in sera of nude mice bearing this tumor (260 pg/ml). Exogenous IL-6 did not enhance the TC-1 cell proliferation as determined by cell count. Flow cytometric analysis could not demonstrate the existence of IL-6 receptor on the cell surface. These results suggested the produced IL-6 did not act as an autocrine growth factor in the cell line. Additional IL-1 alpha to the culture medium induced 3-4 times higher concentration of IL-6 in the culture supernatant compared with that of non-stimulating cells, while exogenous TNF alpha did not stimulate IL-6 production.
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PMID:[Establishment of a new human renal cancer cell line (TC-1) and its productivity of interleukin-6 (IL-6)]. 147 60

Serum concentrations of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) were determined by commercially available enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) in cancer patients treated with recombinant IL-2 (rIL-2) either as 1-h infusion (3 or 5 x 10(6)/m2) or continuous intravenous infusion for 5 days (3 x 10(6)/m2/day). A significant increase of TNF-alpha and IL-6 serum levels was observed in each patient. One-hour infusion of IL-2 induced a very rapid secretion of TNF-alpha, IL-6 and IFN-gamma with considerably higher peak levels than during IL-2 continuous intravenous infusion. IFN-gamma was released into the blood of all patients receiving IL-2 1-h infusion, but only occasionally during or after IL-2 continuous intravenous infusion. Neither IFN-alpha nor IL-1 were detectable in the serum before, during, or following IL-2 treatment in all patients studied. The kinetics of IL-2 after 1-h infusion fitted to a two-compartment model, suggesting the synthesis of considerable amounts of endogenous IL-2. Following IL-2 1-h infusion, rising TNF-alpha serum levels preceded the increase of serum IFN-gamma or IL-6. The serum peak levels of IFN-gamma and IL-6 decreased rapidly with a half-life of 0.29 to 2.5 h. The concentration time profiles of TNF following 1-h infusion of IL-2 demonstrated a considerably longer half-life than that of intravenously administered recombinant TNF as done in other studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid cytokine release in cancer patients treated with interleukin-2. 150 53

The effect of 17 beta-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Addition of 17 beta-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17 alpha-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17 beta-estradiol. 17 beta-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
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PMID:17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. 154 79

Non-isotopic immunoassays for human tumor necrosis factor alpha (TNF alpha) and human interleukin-6 (IL-6) were established by employing the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) system based on the time-resolved fluoroimmunoassay technique with europium-labeled antibody. Compared to enzyme-linked immunosorbent assays and bioassays, the sensitivity and range of measurement were significantly increased by applying the DELFIA systems to TNF alpha and IL-6. TNF alpha was measurable from 100 fg/ml to 10 ng/ml with the TNF alpha-DELFIA and IL-6 was measurable from 100 fg/ml to 1 ng/ml with the IL-6-DELFIA.
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PMID:A new highly sensitive immunoassay for cytokines by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). 156 24

We investigated, in five cell strains per experiment, whether several cytokines known or believed to have effects on bone resorption were produced by nearly homogeneous strains of cultured normal human osteoblast-like (hOB) cells that display virtually the complete phenotype of the mature osteoblast. In unstimulated hOB cells, we detected constitutive production of interleukin-6 (IL-6) (mean +/- SE, 122 +/- 32 pg/ml) and IL-8 (135 +/- 39 pg/ml), but not of IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), or tumor necrosis factor-alpha (TNF alpha). IL-1 beta in doses from 1-100 U/ml stimulated dose-dependent increases in IL-6 (r = 0.87; P less than 0.001) and IL-8 (r = 0.95; P less than 0.001). Similar increases occurred after stimulation with TNF alpha in doses from 3-300 U/ml. IL-1 beta and TNF alpha also stimulated GM-CSF production, but only at higher doses. 17 beta-Estradiol (10(-8) M) had no significant effect on the secretion of any of these cytokines, either constitutively or after stimulation with IL-1 beta or TNF alpha. Stimulated production of IL-4 was not detected after treatment with IL-1 beta or TNF alpha, and that of TNF alpha was not detected after treatment with IL-1 beta. We conclude that IL-6, IL-8, and GM-CSF, but not IL-4 and TNF alpha, are produced by highly differentiated normal human cells of the osteoblast lineage, but their secretion is not regulated by estrogen. However, we cannot exclude the possibility that estrogen regulation of these cytokines may occur during early stages of osteoblast differentiation.
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PMID:Production of various cytokines by normal human osteoblast-like cells in response to interleukin-1 beta and tumor necrosis factor-alpha: lack of regulation by 17 beta-estradiol. 157 80

The correction of chromosomal hypersensitivity to mitomycin C (MMC) in Fanconi anemia (FA) human lymphoblasts is observed by growth in a medium conditioned by normal human cells. Under the same conditions, the cytotoxic effect of MMC on FA cells is restored to an almost normal level. The addition of interleukin-6 (IL-6) to an unconditioned culture medium increased the resistance of FA cells to MMC cytotoxicity. This correcting effect is partially abolished by addition of an anti-IL-6 antibody to the conditioned medium. Both lymphoblasts and fibroblasts derived from FA patients demonstrate a reduction in IL-6 production. Moreover, this lymphokine is not induced by tumor necrosis factors alpha and beta (TNF alpha and TNF beta) in FA cells, as is the case in normal cells. It is suggested that the observed deficiency in IL-6 production may account for one of the major characteristics of FA disease, i.e., the defect in differentiation of the hematopoietic system.
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PMID:Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. I. Involvement of interleukin-6. 157 64

Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL-6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.
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PMID:Interleukin-6 and renal cell cancer: production, regulation, and growth effects. 159 39

The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs injected with physiological saline served as controls. At defined time points before and after each LPS administration venous blood was withdrawn (0, 15, 30, 45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha exhibited an increasing one. IL-6 plasma concentrations increased after each LPS injection. The peak after the third LPS administration, however, was surprisingly low compared to the previous two. The first LPS infusion in our test group led to a significant, sustained rise in mean PAP. After recurrent LPS injections the peak in PAP was not as marked as after the first infusion, indicating the development of a tolerance towards LPS. Initially, CO showed hypodynamic values, whereas the end stage of the experiment was characterized by hyperdynamic CO levels. In conclusion, we believe this porcine model of septic shock to be one of the first large animal models to describe in detail the time-course of various important inflammatory mediators.
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PMID:Time course of various inflammatory mediators during recurrent endotoxemia. 159 96

Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1 beta and/or TNF alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1 beta production. In summary, the ability of IL-6 to potentiate TNF alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis.
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PMID:Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS. 160 43

We have previously reported that tumor necrosis factor-alpha (TNF-alpha) enhances expression of interleukin-6, collagenase, plasminogen activator inhibitor-1, and basic fibroblast growth factor genes in human omental microvascular endothelial (HOME) cells in culture. In this study, we found that treatment of HOME cells with TNF-alpha or interleukin-1 (IL-1) caused enhanced expression of low density lipoprotein (LDL) receptor. A few-fold increase in both LDL binding activity and the receptor mRNA levels was observed when HOME cells were treated with either TNF-alpha or IL-1. Northern blot analysis showed that cellular expression of LDL receptor gene was significantly increased 12-24 h after exposure to TNF-alpha. No significant changes in the life-span of LDL receptor mRNA were observed in untreated and TNF-alpha-treated cells. Scatchard analysis showed an increased receptor number for LDL in TNF-alpha-treated cells. Parallel to increased LDL binding activity, internalization and degradation of LDL were also increased in HOME cells treated with TNF-alpha or IL-1. TNF-alpha-induced enhancement of LDL receptor gene expression was not observed when cycloheximide was present. Cellular mRNA level of SP-1 gene was increased about 3-4-fold at 12 h after treatment with TNF-alpha. Nuclear run-on assays showed increased transcription of LDL receptor gene as well as SP-1 gene by TNF-alpha. Gel retardation assay with the SP-1 consensus fragment showed that SP-1 binding activity was increased about 4-5-fold 12-24 h after treatment with TNF-alpha. NF-kB binding activity was also dramatically increased, but there is no NF-kB motif on the promoter for LDL receptor gene. The induction of LDL receptor by TNF might be mediated through a transcription factor, SP-1.
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PMID:Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. 161 17


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