UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human monocytes were isolated and their ability to harbour growth of virulent tubercle bacilli was assessed, in the presence or absence of various immunomodulators. Calcitriol (1,25(OH2), vitamin D3) alone, at doses of 10(-7)-10(-9) M endowed human monocytes with a significant ability to restrict intracellular growth of the tubercle bacilli. Crude immune lymphokines as well as recombinant interferon-gamma (IFN-gamma) endowed monocytes with no tuberculostatic activity. Similarly, other recombinant cytokines tested, notably colony-stimulating factor-1 (CSF-1), interleukin-1 (IL-1), interleukin-3 (IL-3) and interleukin-6 (IL-6) all failed to stimulate anti-tuberculous properties, and even increased growth of the tubercle bacilli in monocytes, in the case of CSF-1. Conversely, incubation of crude lymphokines in combination with calcitriol led to total stasis of the growth of M. tuberculosis. Experiments with recombinant cytokines and immunologically active vitamins showed that a combination of IFN-gamma tumour necrosis factor-alpha and calcitriol induced a significant amount of intramonocyte killing of M. tuberculosis. Addition of this cocktail of factors to already infected monocytes led to substantial killing of tubercle bacilli. These sets of experiments establish clearly that combinations of recombinant cytokines and vitamins may induce substantial intramonocyte killing of M. tuberculosis. The mechanism involved in this killing activity was not clarified.
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PMID:Killing of Mycobacterium tuberculosis within human monocytes: activation by cytokines and calcitriol. 190 61

We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor-alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony-stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease.
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PMID:Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy. 190 94

The present study was designed to examine the effect of physical exercise on production of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Ten young, healthy volunteers underwent 60-min bicycle exercise at 75% of maximal oxygen uptake (VO2max). Blood samples were collected before and during the last minutes of exercise, as well as 2 h and 24 h later. Blood mononuclear cells (BMNC) were stimulated in vitro with either bacterial lipopolysaccharide or phytohaemagglutinin, and the supernatants were tested for the above-mentioned cytokines using bioassays as well as ELISA techniques. The production of IL-6 increased significantly 2 h after exercise, furthermore the production of IL-1 alpha and IL-1 beta was enhanced, although only borderline significant. TNF-alpha, IL-2 and IFN-gamma did not fluctuate in relation to exercise. The increased amounts of IL-1 and IL-6 in the supernatants generated from a fixed number of BMNC are most likely explained by the increased percentage and absolute number of blood monocytes 2 h after exercise. IL-2 and IFN-gamma are mainly produced by CD4+ and CD16+ cells. During exercise the CD4+ subset decreases, while the CD16+ subset increases. The finding of unchanged production of IL-2 and IFN-gamma was therefore expected.
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PMID:Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma. 190 58

Individual interferon-gamma (IFN-gamma) producing cells in activated human peripheral blood mononuclear cells (PBMC) were characterized by in situ hybridization using [35S]-labelled antisense RNA probes. The proportion of positive cells expressing IFN-gamma mRNA varied according to the substances used for stimulation. IFN-gamma mRNA expressed a relatively low percentage of 1-8% PBMC after a single stimulus with mitogens or OKT-3 antibody and 20-30% of the cells were identified to synthesize IFN-gamma mRNA after stimulation with PHA + P-MA + OKT-3 antibody. The expression of IFN-gamma mRNA and production of the lymphokine was dependent on accessory cells. If accessory cells were replaced by recombinant interleukin-1 (IL-1) plus interleukin-6 (IL-6), then T-cell proliferation to phytohaemagglutinin (PHA) could be partially restored and measurable amounts of IFN-gamma were detected. The addition of interleukin-2 (IL-2) or phorbol-12-myristate-13-acetate to T cells stimulated with PHA, IL-1 and IL-6 did not restore the production of IFN-gamma to an extent comparable to that produced by T cells stimulated in the presence of accessory cells. In further studies, depletion of T-cell subsets showed that CD3+, CD4+, CD8+, CD29+ and CD45RA+ cells were involved in IFN-gamma production after mitogenic stimulation. In conclusion, our data demonstrate that IFN-gamma production is dependent on signals from accessory cells and IFN-gamma is synthesized by only a small proportion of T cells, that did not belong to a unique population, characterized by conventional cellular surface antigens.
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PMID:In situ hybridization of interferon-gamma producing peripheral blood mononuclear cells. 190 64

In previous reports, we demonstrated that adoptively transferred T cells homed to the tumor site (among other sites) and that amplification of immune responses occurred in situ leading to the generation of cytotoxic CD8+ tumor-infiltrating lymphocytes (TIL) and macrophages. The present report extends these findings and shows that following adoptive immunotherapy (AIT) of mice bearing the immunogenic transplanted methylcholanthrene-induced rhabdomyosarcoma (MCA/76-9) there was a differential expansion of CD4+ and CD8+ TIL, the numbers peaking on days 6 and 8, respectively. At this time, CD8+ TIL accounted for the majority of Thy-1+ cells. Northern analyses of RNA extracted from positively selected (by panning) Thy-1+, CD8+ and CD4+ TIL isolated 8 days after AIT indicated the following: in five separate experiments, CD4+ cells expressed three- to sixfold more interleukin (IL)2 mRNA and six- to eightfold more IL6 mRNA than CD8+ cells, while CD8+ TIL expressed three- to sixfold more IL2 receptor (IL2R) mRNA and four- to sixfold more interferon-gamma mRNA than CD4+ cells. TIL cultured in 10% fetal bovine serum failed to release IL2 over a 24-h period, whereas both IL6 and interferon-gamma activities were demonstrable. The level of IL2R mRNA expression was reflected by a vigorous proliferative response of CD8+ TIL to exogenous recombinant IL2 and only a low response by CD4+ cells suggesting that most of the CD4+ TIL were in the resting stage. This was confirmed when it was shown that the incubation of panned CD4+ TIL with IL2 supplemented with irradiated spleen cells and "spent" 76-9 tumor culture supernatant (as a source of antigen) induced expansion of TIL resulting in a population consisting of greater than 90% CD4+ TIL. The overall data suggest that the relatively deactivated state of the CD4+ TIL at this particular time reflects the status of the rejection process in terms of the absence or low concentration of stimulating tumor-associated antigen.
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PMID:Differential in situ expansion and gene expression of CD4+ and CD8+ tumor-infiltrating lymphocytes following adoptive immunotherapy in a murine tumor model system. 190 16

Bone marrow derived macrophages were infected with a virulent strain of Listeria monocytogenes, and the ability of selected cytokines to modify the intracellular growth was assessed. Macrophage monolayers pretreated with either interferon-gamma or tumour necrosis factor were shown to exert a significant listericidal activity. Treatment of monolayers with granulocyte-macrophage colony stimulating factor led to no significant difference in the ability of Listeria to invade and multiply within these cells. Moreover, pulsing of macrophage monolayers with interleukin-6 (IL-6) led to a slight enhancement of Listeria growth in the macrophages, whereas interleukin-4 (IL-4) did not modify Listeria growth. In other sets of experiments, macrophage monolayers were treated with cytokines after phagocytosis of the bacteria. In these conditions, interferon-gamma endowed macrophages with only a modest ability to kill Listeria. Conversely, treatment of monolayers with IL-6 or IL-4 at the time of infection led to expression of high bactericidal activity. Collectively, these results suggest that macrophages may respond to different signals, which enhance their antimicrobial activity before or after infection. Furthermore, B-cell stimulatory factors (IL-4 and IL-6) are potent macrophage-activating molecules.
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PMID:Growth of Listeria monocytogenes in murine macrophages and its modulation by cytokines; activation of bactericidal activity by interleukin-4 and interleukin-6. 191 36

Human monocytes were isolated from the peripheral blood of normal donors and allowed to differentiate in vitro into macrophages. The susceptibility of these cells to infection with a virulent Mycobacterium avium and its modulation by some soluble factors was monitored. The virulent strain of Mycobacterium avium grew progressively in untreated macrophage monolayers. Interleukin-6 (IL-6) was tested for its ability to modulate the macrophage-mycobacteria interaction. Surprisingly, IL-6 was shown to increase M. avium growth in macrophage monolayers by twofold as compared with untreated cells, when added before or after infection. Moreover, addition of rIL-6 to replicating mycobacteria in vitro enhanced their growth two- to three-fold as compared with cultures treated with rIL-6 and a rabbit antiserum to rIL-6. Treatment with IL-6 and interferon-gamma (IFN-gamma) or IL-4 did not modify the growth promoting effect of IL-6 in human macrophages. Overall, our results suggest that IL-6 may contribute significantly to the pathogenesis of infections with M. avium by promoting mycobacterial growth.
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PMID:Recombinant interleukin-6 increases the intracellular and extracellular growth of Mycobacterium avium. 191 52

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.
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PMID:The release of interleukin-1 beta (IL-1) precedes that of interleukin 6 (IL-6) in patients undergoing major surgery. 193 68

Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-gamma (IFN-gamma), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-gamma was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.
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PMID:Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. 195 80

A comparative study was performed to examine the lethal effects of several cytokines injected into mice sensitized with actinomycin D (Act-D). Consistent with published data, human tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) (0.2-5 micrograms) caused the death of the animals within 8-12 hr after injection. Human interleukin-6 (IL-6) and interleukin-8 (IL-8) (0.6-6 micrograms) known to be induced by TNF-alpha did not show any lethal effects, indicating that TNF-alpha-associated lethality is not mediated by IL-6 or IL-8. Human tumor necrosis factor-beta (TNF-beta) (also called lymphotoxin), which shares structural and functional properties with TNF-alpha, was as potent as TNF-alpha in its lethal effects. Murine interferon-gamma (IFN-gamma) (0.04-5 micrograms) was also tested and showed no lethal effects in this model. In addition, a synthetic peptide corresponding to amino acid residues 163-171 of IL-1 beta, and which has been shown to lack the inflammatory effects of IL-1 beta, also caused no lethality among Act-D sensitized mice. The pretreatment of mice with IL-6, IL-8, or IFN-gamma had no protective effects on TNF-alpha or IL-1 beta-induced lethality in contrast to the protection observed by a pretreatment with TNF-alpha/IL-1 beta themselves or with endotoxin. Histopathologic data showed that severe tissue injury in vital organs is associated with the rapid lethality among sensitized mice.
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PMID:Cytokine-associated tissue injury and lethality in mice: a comparative study. 195 40

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