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 ability of interleukin-1 (IL-1) to activate diverse cell populations supports its role as a preeminent cytokine in the pathogenesis of chronic inflammation. In this study, we investigated the role of Il-1 and IL-1 receptor antagonist protein (IRAP) in the regulation of allergen-induced synthesis of IgE and proinflammatory cytokines. The temporal expression of IL-1 beta and IRAP during 5-day allergen-activated peripheral mononuclear cell (PMNC) cultures suggested differential production of the two cytokines. To determine the influence of IRAP on IL-1-mediated cellular responses, we cultured PMNC from allergic donors with specific allergens in the presence or absence of IRAP pretreatment. Culture supernatants were assayed for IgE and cytokines using specific enzyme-linked immunosorbent assay. IRAP at concentrations 0.01, 0.1, and 1 microgram/ml decreased the allergen-stimulated IgE synthesis by 33 +/- 7%, 50 +/- 7%, and 66 +/- 5%, respectively (P < 0.05). Increasing the concentration of allergen did not affect the reduction in IgE synthesis observed in the presence of IRAP. Lipopolysaccharide-stimulated IgE synthesis was also significantly inhibited by IRAP (P < 0.05). In parallel experiments, anti-IL-1 beta monoclonal antibody showed a comparable inhibitory pattern on IgE synthesis (P < 0.05). IRAP inhibited the synthesis of interleukin-6, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor in a dose-dependent manner (P < 0.05); the mean inhibition was 31 +/- 4%, 75 +/- 5%, and 88 +/- 2%, respectively, at 1 microgram/ml of IRAP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 receptor antagonist protein inhibits the synthesis of IgE and proinflammatory cytokines by allergen-stimulated mononuclear cells. 791 15

We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.
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PMID:Involvement of interferon-gamma and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults. 794 64

Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF) were measured in serum and involved and uninvolved skin blister fluids of 20 psoriatic patients and 10 healthy subjects, by enzyme immunoassay. TNF-alpha and IL-6 were always detectable in involved skin blister fluids, while GM-CSF was detected only in 45% of these samples. TNF-alpha, IL-6 and GM-CSF were detected in 95, 100 and 10% of uninvolved skin blister fluid samples, respectively. TNF-alpha and IL-6 were found in 50 and 30% of control blister fluids, while GM-CSF was never detected. In serum, TNF-alpha was detected in 75% of patients and in 70% of controls; IL-6 in 45% of patients and in no controls; and GM-CSF in 35% of patients and in 20% of the controls. The median TNF-alpha and IL-6 levels in involved skin were statistically higher than those of both uninvolved and control skin blister fluids. TNF-alpha and IL-6 levels in blister fluids obtained from both involved and uninvolved skin were higher than those of the patients' sera. GM-CSF, when present in involved skin blister fluids, showed correlated levels with the other cytokines (TNF-alpha: R = 0.85, P = 0.004; IL-6: R = 0.72, P = 0.03). TNF-alpha was highly correlated with IL-6 (R = 0.78, P < 0.00001) in involved skin blister fluids. TNF-alpha and IL-6 levels of involved skin blister fluids showed significant correlations with the psoriasis area and severity index scores in the patients, suggesting a direct relationship between these cytokines and the clinical manifestations of the disease. Moreover, the TNF-alpha levels were particularly related to the erythema scores in the patients, further supporting evidence of their role in the pathogenesis of the disease.
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PMID:Correlated increases of tumour necrosis factor-alpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients--relationships with disease severity. 795 93

When 15-deoxyspergualin (DSG) was administered into [BALB/c-->C3H/He] bone marrow (BM) chimeras from day 14 to day 25, increased platelet counts were observed from day 25 to day 33. Twofold increase of platelet counts was observed in DSG-treated BM chimeras compared with phosphate buffered saline (PBS)-treated BM chimeras. By using reverse transcriptase-polymerase chain reaction (RT-PCR), several cytokine mRNA expressions were analyzed in order to clarify which cytokines are involved in thrombopoiesis. So far, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), stem cell factor (SCF), and IL-11 have been reported to have potent thrombopoietic activity in vivo. Although some other cytokines such as IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) possess the capacity of thrombopoiesis, megakaryocytopoiesis is more marked in these cytokines. IL-6 mRNA expression was increased in spleen cells from DSG-treated BM chimeras from day 25 to day 32 and in bone marrow cells from day 19 to day 28. LIF mRNA expression was not significantly increased compared with PBS control. Although SCF mRNA expression was increased, the kinetics of increased SCF mRNA expression did not fit the kinetics of increased platelet counts. Increased mRNA expression in other hematopoietic cytokines, such as IL-3, granulocyte-colony stimulating factor (G-CSF) and GM-CSF were also observed, thus suggesting that these cytokines may synergistically support thrombopoiesis in concert with IL-6. These results suggest that IL-6 and other hematopoietic cytokines might induce increased platelet counts, although the involvement of thrombopoietin (TPO) and IL-11 should be analyzed in the future.
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PMID:A novel immunosuppressant 15-deoxyspergualin and thrombopoiesis. 795 88

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
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PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29

We analyzed the response of human astrocytoma cell line U373-MG to various cytokines by measuring the production of interleukin-6 (IL6) mRNA and cytokine protein. Interferon gamma (IFN gamma), transforming growth factor beta 1 (TGF-beta 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF) did not induce IL6 mRNA production; however, IL6 mRNA expression and protein production was strongly induced by IL1 alpha and to a lesser extent by IFN alpha. The IL6 mRNA expression induced by IL1 alpha was potentiated by TGF-beta 1 and IFN alpha and slightly decreased by IFN gamma. The potentiation of cytokine mRNA accumulation by TGF-beta 1 was both time- and concentration-dependent. Induction of IL6 mRNA by IL1 alpha was optimally potentiated either if U373-MG cells were pretreated with TGF-beta 1 or if TGF-beta 1 was added within 30 min after stimulation with IL1 alpha. The potentiation of IL6 mRNA by TGF-beta 1 required de novo synthesis of an intermediate protein since treatment with cycloheximide abrogated the amount of mRNA enhanced by TGF-beta 1 without affecting IL1 alpha-driven mRNA production. Nuclear run-on analyses demonstrated increased transcriptional activity of the IL6 gene when stimulated with IL1 alpha in the presence of TGF-beta 1. However, actinomycin-D pulse chase experiments showed that TGF-beta 1 did not increase the stability of IL6 mRNA. Thus, in concert, the results demonstrate that TGF-beta 1 potentiates IL6 production in astrocytoma cells by promoting the transcriptional activity of the IL6 gene and requires coexpression of new proteins. Since cytokines can provide potent mitogenic signals to tumor cells, the results presented here further suggest that the antitumor effect of combination cytokine therapy might partly depend on heterotypic interactions between tumor cells and cytokines.
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PMID:Transforming growth factor beta-1 (TGF-beta 1) potentiates IL1 alpha-induced IL6 mRNA and cytokine protein production in a human astrocytoma cell line. 805 3

Cellular turnover of the hematopoietic system is supported by a small population of cells termed hematopoietic stem cells. Stem cells are capable of self-renewal and differentiation into individual lymphomyeloid lineages. Available evidence indicates that the decision of a stem cell to self-renew or differentiate and the decision of a multipotential progenitor to select a lineage pathway during differentiation (commitment) are intrinsic to the progenitors and are stochastic in nature. In contrast, proliferative kinetics of the progenitors, namely, survival and expansion of the progenitors, appear to be controlled by a number of interacting cytokines. Whereas proliferation and maturation of committed progenitors are controlled by late-acting factors such as erythropoietin, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-5, progenitors at earlier stages of development are controlled by a group of several overlapping cytokines. Interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin-4 regulate proliferation of multipotential progenitors only after they are triggered to exit from dormancy state. Triggering of cycling of dormant primitive progenitors and proliferation of lymphohemopoietic primitive progenitors appear to require interactions of early acting cytokines including interleukin-6, granulocyte colony-stimulating factor, interleukin-11, interleukin-12, leukemia inhibitory factor, and steel factor.
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PMID:Hematopoiesis. 808 74

The expression of receptors for interleukin-6 (IL-6) on human and rhesus monkey peripheral blood and bone marrow (BM) cells was examined by multiparameter flow cytometry after staining with biologically active, biotin-labeled human IL-6 and phycoerythrin-conjugated streptavidin. Consistent with the multiple biologic effects of IL-6 in stimulating immune functions and hematopoiesis, IL-6 receptors were detectable on a wide variety of cell types. In peripheral blood, IL-6 receptors were detectable on monocytes, granulocytes, and on CD4+ T lymphocytes but not on resting, CD19+ B lymphocytes and CD56+ natural killer (NK) cells. CD8+ T lymphocytes also expressed IL-6 receptors but at lower levels than CD4+ cells. The IL-6 receptors on granulocytes were only detectable after staining with high concentrations of biotin-IL-6, suggesting that most IL-6 receptors on these cells represent low-affinity sites. In contrast, IL-6 receptors on both CD4+ and CD8+ T lymphocytes were detectable at biotin-IL-6 concentrations as low as 10 pmol/L, indicating that these cells bind IL-6 with high affinity. IL-6 receptor expression patterns on rhesus monkey and human blood cells were very similar except that receptor levels on granulocytes were lower in humans than in rhesus monkeys. Similar differences in expression levels were observed for IL-6 receptors that were detectable on most granulocyte precursors in the mononuclear fraction of rhesus monkey and human bone marrow. In addition to these relatively mature cell types, IL-6 receptors were detectable on a large fraction of human and rhesus monkey BM blast cells that express the CD34 antigen. The presence of IL-6 receptors on CD34+ BM blast cells, which are the precursor cells of most, if not all, BM-derived blood cells, is consistent with the ability of IL-6, in conjunction with other cytokines, to stimulate immature hemopoietic cells in vitro and to promote blood cell production when administered in vivo.
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PMID:Flow cytometric detection of receptors for interleukin-6 on bone marrow and peripheral blood cells of humans and rhesus monkeys. 809 19

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
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PMID:Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. 811 34

Five cell lines were established from four undifferentiated carcinomas and one squamous cell carcinoma of the thyroid. The levels of several kinds of cytokines were measured in the conditioned media of these cell lines by enzyme-linked immunosorbent assay (ELISA). Interleukin-6 (IL-6) was produced by four of the five cell lines, interleukin-1 alpha (IL-1 alpha) by three cell lines, and granulocyte-colony stimulating factor (G-CSF) by two cell lines. The mRNA of IL-1 alpha or IL-6 was detected by Northern blot analysis in all the cell lines which secreted these cytokines into culture medium. These results suggest that undifferentiated carcinoma and squamous cell carcinoma of the thyroid frequently produce cytokines. Further studies are needed to clarify the possible clinical effects of these cytokines in patients with thyroid carcinoma.
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PMID:Production of cytokines by thyroid carcinoma cell lines. 812 Nov 82


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