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)

Inflammatory processes are characterized by increased levels of extracellular phospholipase A2 (PLA2) and cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF). IL-1, TNF and PLA2 share a number of proinflammatory, arthritogenic effects. The sequential induction, first of the cytokines followed by PLA2, suggests that these cytokines may regulate synthesis and secretion of PLA2. To test this postulate, foetal rat calvarial bone-forming cells (FRCC) were treated with recombinant human IL-1 and TNF and extracellular PLA2 release was quantitated. Both IL-1 and TNF induced the de novo synthesis of PLA2 in a concentration-dependent manner. Continuous exposure of FRCC in primary culture to IL-1 (50 units/ml) over 15 days resulted in as much as 100-fold increase in PLA2 secretion. IL-1 (50 units/ml) added to post-confluent cultures for a 48-h pulse increased PLA2 activity 9.4-fold. The combination of IL-1 (50 units/ml) and TNF (500 units/ml) was synergistic with an observed increase in extracellular PLA2 secretion of 146-fold following a 48-h pulse. Interleukin-6, alone or in combination with IL-1 or TNF, did not further enhance PLA2 synthesis of secretion. Cytokine-induced synthesis of PLA2 was inhibited 80% by 10 microM cycloheximide but not by dexamethasone over the range of 10(-6) to 10(-8) M. FRCC-derived PLA2 was neutral-active with a pH optimum of 6-7.5 and was calcium-dependent with optimal activity in the presence of 2-7 mM calcium. It had absolute 2-acyl specificity using micellar phosphatidylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action. 188 15

The participation of interleukin-6 (IL-6) in the pathophysiology of normal and abnormal human parturition was evaluated by determining IL-6 concentrations in amniotic fluid (AF). Biologically active IL-6 was determined (in U/ml) using the B9 hybridoma growth factor assay, while the concentrations of immunoreactive IL-6 species (in pg/ml) were assessed using a monoclonal antibody (moAb)-based ELISA. Two hundred and twenty-seven AF samples from women in normal labor and from those presenting with a clinical diagnosis of premature rupture of membranes (PROM) were assayed. In selected instances, IL-6 levels were evaluated simultaneously in AF and in maternal and fetal plasma. Women with a normal pregnancy had low titers of biologically active IL-6 in AF both at midtrimester (group 1, n = 27; median IL-6 concentration = 16 U/ml) and at term (group 2, n = 33; median = 15 U/ml). There was an increase in the IL-6 bioactivity in AF from women in normal labor at term (group 3, n = 40; median = 74 U/ml; p less than 0.001). In order to distinguish between the relative contributions of parturition per se and of intrauterine infection to the elevation of biologically active IL-6 levels in AF, IL-6 titers were compared in four different groups of women with PROM.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytokine 1991 Mar
PMID:Cytokines in normal and abnormal parturition: elevated amniotic fluid interleukin-6 levels in women with premature rupture of membranes associated with intrauterine infection. 188 85

Interleukin-6 (IL-6) activates (2'-5') A synthetase (2'-5' AS) gene expression in differentiating myeloleukemic M1 cells. Antibodies to type I interferon (IFN) inhibit 2'-5' AS induction but not differentiation. Analysis of the mechanism of 2'-5' AS induction shows that it does not result from increased IFN formation, but from a synergism between IL-6 and endogenously secreted IFN. IL-6 can activate expression of a CAT construct fused to the interferon response sequence (IRS) of the 2'-5' AS gene. In extracts of IL-6-treated M1 cells, changes in protein binding to IRS DNA can be demonstrated. One of the effects of IL-6 on M1 cells is, therefore, to induce DNA binding factors, some of which act on the same enhancer sequence as IFNs, resulting in a synergistic gene activation. M1 variants resistant to differentiation by IL-6 have lost the ability to induce the 2'-5' AS gene.
Cytokine 1991 Mar
PMID:Interleukin-6 induces the (2'-5') oligoadenylate synthetase gene in M1 cells through an effect on the interferon-responsive enhancer. 188 86

Analysis of the number of receptors per cell and the affinity of the ligand/receptor interaction has provided considerable insight into the functioning of numerous cytokines. Interleukin-6 (IL-6) is a multifunctional cytokine which may have considerable clinical relevance in inflammatory or immunodeficiency diseases. Using particle concentration fluorescence immunoassay (PCFIA) technology, an assay is described which calculates the receptor number and affinity on small numbers of human cells. Resting B cells are shown to lack IL-6 receptors but activation of B cells induces up to 1,300 receptors per cell, with Kd of 1 x 10(-11) to 2 x 10(-11) M. Other recombinant mediators do not alter the binding of labeled IL-6 to the cells. PCFIA avoids the use of radioactivity and requires very small numbers of cells (2 x 10(4) per well). Potential application to the study of regulatory mechanisms and to clinical situations where small samples of blood are available is feasible.
Cytokine 1991 Jan
PMID:Particle concentration fluorescence immunoassay for measuring interleukin-6 receptor numbers. 190 91

Culture of Peyer's patch (PP) B cells with interleukin-6 (IL-6) for 7 days results in a six- to eightfold increase in secretion of IgA, while little or no increase in IgM or IgG secretion occurs in these cultures. Further, greater than 80% of IgA is produced within the first 72 h of culture. Using a sensitive enzyme-linked immunospot (ELISPOT) assay, we have shown that culture of PP B cells with IL-6 for 24 h gave increased IgA spot-forming cells (SFC) (4- to 6- fold) even though secreted IgA, as measured by RIA, had only increased 1.6- to 2.0-fold. In addition, significant increases in IgA SFC numbers could be demonstrated as early as 4 h after addition of IL-6. The increase in IgA secretion was not the result of IL-6-induced B-cell proliferation, since culture of B cells with IL-6 resulted in no increase in [3H]thymidine incorporation compared to untreated controls. This was supported by studies with mitomycin C which, when added to B cell cultures, had no effect on the IL-6-induced increase in numbers of IgA SFC. Increased IgA secretion was totally abolished by actinomycin D, an inhibitor of RNA transcription, showing that continued production of alpha mRNA is essential for IL-6-induced IgA secretion. Separation of PP B cells into peanut agglutin (PNA)Hi (germinal center [GC]) and PNALo (non-GC) subpopulations before culture with IL-6 showed that only PNALo B cells transcribe increased levels of alpha mRNA message and secrete high levels of IgA in response to this cytokine. Although the GC are the site of B-cell proliferation and presumably of switching to IgA and contain 70 to 85% of sIgA+ B cells in the PP, these PNAHi B cells do not respond to IL-6. This suggests that memory sIgA+ B cells in PP express IL-6 receptor (IL-6R) and respond to this cytokine with rapid differentiation into plasma cells that secrete IgA.
Cytokine 1991 Mar
PMID:Peyer's patch B cells with memory cell characteristics undergo terminal differentiation within 24 hours in response to interleukin-6. 190 87

The cytokine response to major surgical trauma has been studied in six patients undergoing elective aortic surgery. Peripheral blood was sampled frequently before, during, and after surgery and the plasma cytokines interleukin-1, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were measured using enzyme-linked immunosorbent assays. These results were reviewed together with the operative details, clinical course, and C-reactive protein levels. Tumor necrosis factor-alpha and interferon-gamma were not detected in these patients. An early and short-lived interleukin-1 beta response to major surgery was detected only by intensively sampling the intraoperative period. This was a consistent finding that preceded the rise in interleukin-6. Interleukin-6 rose steeply from 2 h, peaking between 4 and 24 h. It had fallen sharply by 48-72 h in five patients who had an uneventful postoperative course. It remained high in one patient who developed complications and fell only when a severe septicemia was treated successfully. His interleukin-6 levels were considerably higher than the other patients even during the operation itself. There was no obvious relation between the interleukin-6 peak and the duration of operation. A sequential interleukin-1 beta and interleukin-6 response has not been noted before in vivo, and would seem to provide evidence supporting the in vitro observation that interleukin-1 induces interleukin-6 synthesis and release. It also provides evidence of an important role for interleukin-6 in the body's response to injury. A larger study is in progress.
Lymphokine Cytokine Res 1991 Aug
PMID:The release of interleukin-1 beta (IL-1) precedes that of interleukin 6 (IL-6) in patients undergoing major surgery. 193 68

We investigated the capacity of mouse bone marrow-derived macrophages (BMDM) to produce interleukin 1 (IL 1), interleukin-6 (IL 6), and tumor necrosis factor (TNF) upon lipopolysaccharide (LPS) stimulation. BMDM were allowed to differentiate either in the presence of conditioned medium (from WEHI-3 or L cells), or in the presence of recombinant cytokines (IL 3, macrophage-colony stimulating factor [M-CSF], or granulocyte/macrophage-colony stimulating factor [GM-CSF]). Cells were maintained in culture up to 3 weeks and tested at different times. Significant spontaneous cytokine production was never observed. BMDM rapidly acquired the capacity to elaborate cytokine upon LPS activation. LPS-triggered BMDM were able to produce IL 1, IL 6, and TNF, throughout the culture period, although 2- to 3-week-old cells lost their ability to release IL 1 while accumulation of intracellular IL 1 remained unchanged. The dissociation between synthesis and release of IL 1 was not correlated with a significant modification of the specific binding of LPS onto the cell surface.
Cytokine 1990 Jul
PMID:Lipopolysaccharide-induced production of cytokines by bone marrow-derived macrophages: dissociation between intracellular interleukin 1 production and interleukin 1 release. 210 27

Treatment of the AML-193 leukemic cell line with phorbol myristate acetate (PMA) resulted in the loss of their ability to proliferate in response to GM-CSF or IL-3. This was not due to a change in number or affinity of GM-CSF receptors, but possibly resulted from an other cellular mechanism. The AML-193 differentiated cells acquired the ability to phagocytose glutaraldehyde-fixed E.coli in a similar fashion to mature macrophages. In addition the PMA-differentiated AML-193 cells now secreted a factor which specifically inhibited the binding of interleukin-1 (IL-1) to its receptor on the murine thymoma cell line EL-4.6.1C10. The synthesis of this inhibitor was further increased by the addition of GM-CSF or IL-3. Pulse labelling experiments showed that this activity was due to a 26 kDa protein that bound to the IL-1 receptor even in the presence of neutralizing antibodies against IL-1 alpha or IL-1 beta, and this binding was only antagonized by IL-1 alpha or IL-1 beta. In contrast, peripheral monocytes obtained from the blood of normal donors, when induced with either GM-CSF or IL-3, produced large quantities of inhibitor in the absence of PMA. This report clearly shows that a leukaemic cell line can respond to GM-CSF and IL-3 in different ways before and after in vitro differentiation.
Eur Cytokine Netw
PMID:Granulocyte-macrophage colony stimulating factor and interleukin-3 regulate the production of an interleukin-1 inhibitor by the differentiated AML-193 leukemic cell line. 215 93

The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated.
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PMID:Biological response to intravenously administered endotoxin in patients with advanced cancer. 225 60

The intrathyroidal production of Interferon gamma, tumour necrosis factor alpha and beta, Interleukin-1 alpha and beta, Interleukin-6, platelet-derived growth factor A and of transforming growth factor-beta was analysed in patients with autoimmune and non-autoimmune thyroid disease. Cytokines were assessed indirectly by slot blot mRNA analysis in fresh tissue samples (unpurified cells, infiltrating mononuclear cells and thyroid follicular cells), in thyroid follicular cells in primary culture, as well as in thyroid-derived T-cell clones. The production of Interleukin-1 alpha and beta, Interleukin-6 and transforming growth factor beta was additionally measured by bioassay. Cytokine production by thyroid-infiltrating mononuclear cells generally did not differ between autoimmune and non-autoimmune samples, the whole panel of all cytokines being found in freshly purified cells as well as in thyroid-derived T-cell clones from patient with Graves' disease, as well as with multinodular non-toxic goitre. Thyroid follicular cells produced Interleukin-1 alpha, Interleukin-6 and transforming growth factor beta. Interleukin-1 and Interleukin-6 production did not differ between thyroid follicular cells from autoimmune and non-autoimmune thyroids. Transforming growth factor beta was, however, lower in non-toxic goitre than in Graves' disease and in normal thyroid tissue, but could be increased by exposure of the cells to micromolar concentrations of iodide. This seemed of special interest, as transforming growth factor beta proved to inhibit thyroid follicular cell growth in response to known growth stimuli, such as insulin-like growth factor I or epidermal growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intrathyroidal cytokine production in thyroid disease. 267 71


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