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 production by monocytes of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNF alpha and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-1 alpha is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1 beta were lower than those of TNF alpha. Cell-associated IL-1 beta and TNF alpha were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-1 alpha production by monocytes in all patients, and of IL-1 beta, IL-6, and TNF alpha in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections.
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PMID:Dysregulation of in vitro cytokine production by monocytes during sepsis. 193 59

Plasma levels of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were monitored after intravenous administration of Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNF alpha concentrations with maximal levels at 90 min (369 +/- 44 pg/ml, P less than .001 vs. saline controls, n = 7). The rise in TNF-alpha was followed by a rise in plasma IL-6 (27 +/- 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with ibuprofen (n = 6) caused a significant augmentation and temporal shift in cytokine elaboration with maximal TNF alpha levels (627 +/- 136 pg/ml) at 120 min and IL-6 peaks (113 +/- 66 ng/ml) at 180 min. In ibuprofen-treated volunteers, the additional increase in TNF alpha was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenase inhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulation.
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PMID:Pretreatment with ibuprofen augments circulating tumor necrosis factor-alpha, interleukin-6, and elastase during acute endotoxinemia. 198 81

The human leukemic cell line AML-193 was tested for its proliferative response to endogenously produced autocrine factors and to a variety of cytokines and colony-stimulating factors. Cells grown in the absence of GM-CSF incorporated tritiated thymidine, and this was partially reversed by adding neutralizing anti-GM-CSF antibodies to the culture medium, suggesting that it was due, at least in part, to autocrine GM-CSF production. This was confirmed by immunopurification of a GM-CSF-like activity from cell supernatant of AML-193 cells grown in serum free medium in the absence of exogenous GM-CSF. When AML-193 cells were cultured with GM-CSF in combination with other cytokines, Interleukin-1 alpha and beta (IL-1 alpha and beta), Interleukin-3 (IL-3), Interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha), none of them affected the concentration of GM-CSF required to induce 50% of maximum proliferation (D50). However, the maximum proliferation induced by GM-CSF alone was drastically decreased by IL-1 alpha, IL-1 beta and TNF alpha. Inhibition caused by exposure of the AML-193 to IL-1 for up to 24 hr was reversible, ruling out a direct cytotoxic effect.
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PMID:Growth regulation of the AML-193 leukemic cell line: evidence for autocrine production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and inhibition of GM-CSF-dependent cell proliferation by interleukin-1 (IL-1) and tumor necrosis factor (TNF alpha). 199 54

It was recently reported that the opiate antagonist, naloxone (Nal), blocks the changes induced by the endogenous pyrogen, interferon-alpha 2 (IFN), in the electrical activity of hypothalamic thermosensitive neurons in rat brain slice preparations. This study was undertaken to determine whether the pyrogenic response to this cytokine might, therefore, be modulated through Nal-reversible opiate receptors. To examine this possibility, conscious guinea pigs were injected IV with recombinant human (rh) IFN (10 MU/animal), or, for comparison, with S. enteritidis endotoxin (lipopolysaccharide, LPS; 2 micrograms/kg), rh tumor necrosis factor-alpha (TNF; 20 micrograms/kg), or rh interleukin-6 (IL6; 50 micrograms/kg); Nal (10 mg/kg, SC) was administered immediately before the pyrogens. And also for comparison, in separate experiments, indomethacin (Indo; 10 mg/kg, IM) was injected 20 min before the pyrogens. Both Nal and Indo abolished the febrile rises evoked by IFN, TNF, and IL6. Nal reduced the first and suppressed the second of the characteristically bimodal febrile response to LPS; Indo depressed both peaks. Neither blocker had any significant thermal effect by itself. These results suggest that two processes may mediate the pyrogenic effects of these substances, viz., an endogenous opioid- and a PGE-dependent mechanism.
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PMID:Neuromodulation of fever: apparent involvement of opioids. 201 82

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
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PMID:Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. 204 24

Epithelial cells both produce and are affected by interleukin-6 (IL-6). Experiments with an adenocarcinoma-derived cell line (HeLa) reveal that activation of the transfected human IL-6 promoter occurs largely through two partially overlapping second messenger (cAMP, phorbol ester)- and cytokine (IL-1, TNF, serum)-responsive enhancer elements (MRE 1, -173 to -151 and MRE II, -158 to -145). MRE I contains the typical GACGTCA cAMP and phorbol ester-responsive (CRE-TRE) motif, whereas MRE II defines a new CRE/TRE motif that contains an imperfect dyad repeat. The mechanism of dexamethasone-mediated repression of IL-6 gene expression in epithelial cells involves occlusion of the entire MRE enhancer region and of the core-promoter elements (TATA-box and RNA start site) by ligand-activated glucocorticoid receptor. Enhanced levels of IL-6 expression are observed in many solid tumors and in the hyperproliferative (and glucocorticoid-suppressible) lesions of psoriasis. In cell culture, IL-6 enhances, inhibits, or has no effect on the proliferation of epithelial cells depending upon the cell-type examined. IL-6 enhances proliferation of keratinocytes but inhibits that of breast carcinoma cell lines ZR-75-1 and T-47D. In these breast carcinoma cells, IL-6 elicits a major change in cell phenotype which is characterized by a fibroblastoid morphology, enhanced motility, increased cell-cell separation, and decreased adherens type junctions (desmosomes and focal adhesions). The new data identify IL-6 as a regulator of epithelial cell growth and of cell-cell association.
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PMID:Expression and function of interleukin-6 in epithelial cells. 204 25

In a previous study, we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term dialyzed patients and that of tumor necrosis factor alpha (TNF alpha) in both long-term and not yet dialyzed uremic patients. In the present study, we attempted to determine the respective influence of hemodialysis (HD) and uremia on the plasma level of interleukin-6 (IL-6), which shares several biological properties with IL-1 and TNF alpha, including the induction of the acute phase response of the inflammatory process. Forty-eight patients with end-stage renal failure, including 32 long-term HD patients and 16 chronic uremic patients undergoing their first dialysis session, were tested for plasma IL-6 using both biological and immunoreactive assays. Plasma IL-6 activity was significantly increased in patients with chronic renal failure (P less than 0.001) compared to its level in normal individuals. No difference was observed, however, between long-term and not yet dialyzed patients. In the patients with the most pronounced IL-6 activity, immunoreactive IL-6 levels between 60 and 150 pg/ml were detected. A monoclonal antibody (mAb) against human IL-6 inhibited the activity of plasma in the IL-6 bioassay, and a close correlation existed between the biological activity of IL-6 and its immunoreactive level. No change in plasma IL-6 was detected during the course of the first dialysis as well as subsequent sessions. Likewise, no influence of the nature (cellulosic or synthetic polyacrilonitrile) of the dialysis membrane equipping the dialyzer was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated circulating levels of interleukin-6 in patients with chronic renal failure. 206 12

Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) are pluripotent cytokines mediating the host response to sepsis, injury, and cancer. Animals can be protected from the lethal effects of TNF alpha by repeated administration of sublethal doses, but the mechanism of this effect is not known. Human foreskin fibroblasts (FS4 cells), which rapidly elaborate interleukin-6 (IL-6) when stimulated with TNF alpha or IL-1 alpha, were grown in culture as confluent monolayers and their secretion of IL-6 was quantitated using the murine B9-hybridoma bioassay against an external reference of human recombinant IL-6 (Genetics Institute). When FS4 cells were incubated with human recombinant TNF alpha (50 ng/ml; Cetus) or recombinant IL-1 alpha (30 pg/ml; Genzyme) a rapid increase in IL-6 production was measured over control, rising to IL-6 levels of 71.7 +/- 5.9 units/ml with TNF alpha and 54.0 +/- 1.2 units/ml with IL-1 alpha after 7.5 hr incubation. FS4 cells which were exposed to cytokine, rinsed, and then reexposed to cytokine 24 hr later produced significantly less IL-6 [38.1 +/- 2.8 units/ml with second exposure to TNF alpha (P less than 0.05), and 18.3 +/- 1.9 units/ml with second exposure to IL-1 alpha (P less than 0.01)]. Successive daily exposure to TNF alpha or IL-1 alpha caused a further stepwise diminution of IL-6 secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased IL-6 secretion by fibroblasts following repeated doses of TNF alpha or IL-1 alpha: post-transcriptional gene regulation. 206 55

Previous studies have demonstrated considerable prostanoid production by cultured proliferating rat mesangial cells (MC). In this study, human mesangial cells (HMC) were examined during serum-free culture in which the cells were reversibly growth arrested and did not suffer obvious irreversible functional changes. Non-stimulated cells released 2 to 10 pg/24 hr/micrograms cellular protein of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, while TXB2 was not detectable. Stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) induced up to 18-fold (IL-1 beta) or up to fourfold (TNF alpha) increases of prostanoid release. Combinations of the two monokines resulted in significant synergistic induction of PGE2 and 6-keto-PGF1 alpha up to 38 times that of control cells. Interleukin-6 (IL-6) and the HMC-mitogen, platelet-derived growth factor-BB (PDGF-BB) only induced marginal increases in HMC prostanoid generation. However, when PDGF-BB or -AB was combined with IL-1 beta or IL-6, prostanoid generation by HMC was synergistically increased up to 222-fold (IL-1 beta) or 12-fold (IL-6) above the control values, with the induction of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha much greater than TXB2. In the case of IL-1 beta + PDGF-BB the induction of PGE2 release was at least partly due to the synergistic induction of cyclooxygenase activity. These findings demonstrate that both proliferating and reversibly growth arrested HMCs release prostaglandins in response to various inflammatory stimulators and combinations thereof. The findings support the important role of HMC in the regulation of glomerular hemodynamics during inflammatory processes.
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PMID:Monokines and platelet-derived growth factor modulate prostanoid production in growth arrested, human mesangial cells. 210 53

Affinity chromatography of crude human urinary proteins on either human recombinant interleukin-6 (rIL-6) or human recombinant interferon-gamma (rIFN-gamma) or anti IFN-gamma receptor (IFN-gamma-R) monoclonal antibodies (McAb) yielded the two respective soluble receptors in significant amounts. A single sequence of 30 amino acid residues was obtained by N-terminal microsequencing of the protein peak purified in tandem by affinity chromatography on an IL-6 column and reversed-phase high-performance liquid chromatography. This sequence was identical with the predicted N-terminal sequence of IL-6-R as previously reported. The purified IL-6-R retained its biological activity. It was used for the preparation of specific anti IL-6-R monoclonal antibodies. Analysis of the eluted proteins from both IFN-gamma and anti IFN-gamma-R columns by inhibition of solid-phase radioimmunoassay, enzyme-linked immunosorbent assay, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting proved the existence of soluble IFN-gamma-R in normal urine. This finding together with the already known presence of soluble TNF receptors and a soluble IL-2 receptor found both in plasma and in urine indicates that release of soluble cytokine receptors into body fluids is a general phenomenon which occurs under normal physiological conditions.
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PMID:Purification of soluble cytokine receptors from normal human urine by ligand-affinity and immunoaffinity chromatography. 214 54


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