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)

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast-cells, macrophages, fibroblasts) during wounding, cutaneous allergy and infections. We have previously demonstrated that following stimulation with interleukin-4 (IL-4) or interferon-gamma, human EK express the low affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody, induces a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, as this is completely abolished by cAMP or NO synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.
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PMID:IgE-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes: the role of cAMP and nitric oxide. 924 2

We generated > 10(7) mast cells by culturing 10(7) cord blood mononuclear cells for > 10 weeks in the presence of Steel factor, interleukin-6 and prostaglandin E2. 99% of the cultured cells had tryptase-positive granules, while 18% had chymase-positive granules. Cultured mast cells contained 3.6 micrograms histamine and 3.5 micrograms tryptase per 10(6) cells. Cells sensitized with 1 microgram/ml human IgE released 58.5% histamine and 1.55 ng tumor necrosis factor (TNF)-alpha per 10(6) cells when challenged with 1 microgram/ml antihuman IgE, whereas the control cells spontaneously released 3.7% histamine and 0.18 ng TNF-alpha. Analysis for surface antigens revealed that cultured mast cells expressed the following CD molecules: 9, 13, 14, 29, 33, 38, 43, 44, 45RA, 45RB, 46, 47, 48, 49d, 50, 51, 53, 54, 55, 58, 59, 60, 61 and 117 (c-Kit). Taken together, these cultured cells seem to be functionally mature mast cells.
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PMID:Characterization of cord-blood-derived human mast cells cultured in the presence of Steel factor and interleukin-6. 754 4

Although stem cell factor (SCF) has been identified as a critical cytokine for the development of human mast cells from their progenitors, the effects of other cytokines on human mast cells are less well understood. We examined the effects of several cytokines on the survival of human mast cells of 100% purity generated in suspension cultures of umbilical cord blood mononuclear cells in the presence of 100 ng/mL recombinant human (rh) SCF and interleukin-6 (IL-6). Mast cells suspended in conventional serum-containing medium died over a period of 2 to 6 days after the withdrawal of SCF and IL-6. The cells became pyknotic and underwent DNA fragmentation characteristic of apoptosis. The addition of SCF, IL-3, IL-4, IL-5, or IL-6 to the cultures in both serum-containing and serum-free medium prolonged their survival in a dose-dependent manner. Some other cytokines, such as IL-2, IL-9, IL-10, IL-11, tumor necrosis factor-alpha, transforming growth factor-beta 1, and nerve growth factor, had no survival-promoting effect at 100 ng/mL. Preincubation of mast cells with SCF, IL-4, IL-5, or IL-6 for 24 hours during sensitization with IgE enhanced IgE/anti-IgE antibody-induced histamine release from mast cells, whereas IL-3 showed a negligible effect. Polymerase chain reaction amplification of alpha-chains of IL-3 receptor (R), IL-4 R, IL-5 R, and IL-6 R yielded products of the correct size predicted from the sequence of each receptor. The binding assay using 125I-labeled IL-3 indicated that these mast cells bear receptors for IL-3. These findings suggest that IL-3, Il-4, IL-5, and IL-6, which are mainly produced by T-helper 2 lymphocytes, might regulate the functions of human mast cells in vivo via specific receptors in allergic reactions.
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PMID:Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6 on the survival of cultured human mast cells. 757 37

Pruritus is a very common complication in chronic hemodialysis (HD) patients, however the exact mechanism for this affliction is still not known. Anti-histaminics usually failed to alleviate uremic pruritus. In others, an anti-allergic drug, which inhibits the release of chemical mediators, such as leukotrienes or histamine from mast cells, was reported to be effective. We evaluated the values of leukotriene B4 and interleukin 6 in HD patients with pruritus and the effect of an anti-allergic drug on these factors. Leukotriene B4, interleukin-6, C3a, C5a, the number of eosinophil and IgE at 0, 15 and 180 minutes after the start of regular HD in 11 HD patients suffering from pruritus and as well as in 11 HD patients without pruritus were examined. These HD patients in both groups showed significantly higher (p < 0.001) values of leukotriene B4 and C3a compared to healthy non-HD subjects. There was no difference in the leukotriene B4, interleukin-6, IgE, C3a and C5a levels between the patients with and without pruritus. Two mg/day of azelastin hydrochloride, an anti-allergic drug was orally given to the pruritus group for 3 weeks. In 5 of 11 patients, the pruritus symptoms disappeared, while in 4 of 11 they improved. Independent of the effect of the drug on pruritus, leukotriene B4 levels significantly decreased compared with those before the administration of this drug in the pruritus group (p < 0.01). Interleukin 6, C3a, C5a and the number of eosinophils demonstrated no significant change. In conclusion, although azelastin hydrochloride was effective in treating pruritus and also suppressed leukotriene B4 levels in hemodialysis patients, the high leukotriene B4 activity itself did not seem to be related to the development of pruritus in these patients.
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PMID:The effect of azelastin hydrochloride on pruritus and leukotriene B4 in hemodialysis patients. 759 27

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

Two 4- and 5-year-old children suffering from refractory atopic dermatitis were treated with recombinant interferon-gamma (rIFN-gamma). rIFN-gamma was injected at 50 micrograms subcutaneously three times a week in the first child for 3 weeks, followed by three times 25 micrograms in week 4. In the other child two treatment courses of 4 weeks were given after a break of 2 weeks. Therapy was well tolerated. In child one reductions in eczematous body surface and severity of lesions were observed, while no beneficial effect was seen in the other. Clinical chemistry data remained unchanged. Immunological studies performed in parallel showed a decrease in total serum IgE of 50% in child 1, a decrease in spontaneous in vitro IgE production, an increase in in vitro production of interleukin-6, and a normalization of previously decreased in vitro lymphocyte responses to several mitogens. While marked immunological changes were noted during IFN-gamma treatment, clinical benefits were not encouraging. Diminished IFN-gamma production has been claimed to be a major pathogenic factor in atopic eczema. Our results indicate that the pathogenesis is more complex. Clinically, we were unable to confirm previous observations in adults. Further studies are needed before IFN-gamma can be recommended for therapy of pediatric atopic eczema.
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PMID:Interferon-gamma for treatment of severe atopic eczema in two children. 808 77

The allergen extracts of wheat, rye, barley and oats flours were characterized by IgE-immunoblotting with serum samples from 40 adult patients; 35 patients with atopic dermatitis, one with rhinitis and four with urticaria. All these patients had been positive when skin-prick testing was carried out with one or more of the four flour extracts or displayed one or more positive cereal RAST results. Four non-atopic sera were used as negative controls. Acidic and neutral protein extracts of wheat, rye, barley and oats flours were processed for the immunoblotting experiments and 35 patients appeared positive in IgE immunoblotting with wheat and rye, 32 with barley and 33 with oats. The IgE immunoblots showed polyspecific binding patterns; wheat exhibited 36 IgE stained bands, rye 35, barley 33 and oats 10. Eighteen of the IgE stained bands could be classified as intermediate allergens for wheat, 23 for rye and 15 for barley. The 66 kDa protein in oats was visualized by 28 out of 33 sera (84%), however, there was evident non-specific binding to this region and thus it may also represent lectin-like binding. The most frequent staining with wheat extract was seen in the 26 kDa protein region (15/35, 43%), with rye in the 40 kDa (16/35, 46%) and with barley in the 26 and 46 kDa protein bands (14/32, 44%). Simultaneous staining with wheat, rye and barley extracts were observed with 16 bands suggesting crossreactivity between these cereals.
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PMID:IgE-binding components of wheat, rye, barley and oats recognized by immunoblotting analysis with sera from adult atopic dermatitis patients. 808 61

The basophilic leukaemia cell line KU812 can be induced to differentiate into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, produce histamine and tryptase and have the capacity for IgE-mediated histamine release. In this study we have examined the cytokines, produced by the Mo cell line, which are responsible for the observed differentiation-inducing effect in the KU812 cell line. It was shown that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were responsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line. Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors indicating induction of these receptors during differentiation. Spontaneous differentiation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The activity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.
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PMID:TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812. 813 23

Trypanosoma cruzi infection of mice triggered endogenous production of interleukin-6 (IL-6) during the ascending phase of parasitemia. Injections of anti-IL-6 monoclonal antibody in infected mice at the time of the serum IL-6 peak paradoxically increased IL-6 levels to 60- to 80-fold those in infected mice receiving unrelated immunoglobulins. This early and transient increase in circulating IL-6 levels modified neither the immunoglobulin nor T. cruzi-specific antibody levels of immunoglobulin G1 (IgG1), IgG2a, IgG3, IgM, IgA, and IgE isotypes or the final outcome of infection nor the blood or tissular parasite levels. However, it tended to delay mortality of mice and to increase the levels of the acute-phase protein serum amyloid P component.
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PMID:Interleukin-6 (IL-6) production in mice infected with Trypanosoma cruzi: effect of its paradoxical increase by anti-IL-6 monoclonal antibody treatment on infection and acute-phase and humoral immune responses. 830 Feb 26

Interleukin-6 (IL-6) is a cytokine that acts on a variety of cell types, including myeloid progenitor cells and B and T lymphocytes. It has been found to activate cytotoxic T cells and natural killer (NK) cells and to induce T-cell-mediated antitumour effects in animal models. In a phase I clinical trial of recombinant human IL-6, 20 patients with advanced cancer were entered to receive daily subcutaneous injections of IL-6 over 7 days followed by a 2-week observation period and another 4 weeks of daily IL-6 injections. Doses varied between 0.5 microgram/kg and 20 micrograms/kg body weight and immune functions were monitored throughout. At all dose levels IL-6 administration led to a marked increase in serum levels of C-reactive protein and a moderate rise in complement factor C3. The proportions of CD4, CD8 or HLA-DR lymphocytes in peripheral blood did not alter with IL-6 treatment nor did the in vitro proliferation of peripheral blood mononuclear cells induced by either phytohaemagglutinin, pokeweed mitogen or fixed Staphylococcus aureus. By contrast, NK cell activity, lymphokine-activated killer (LAK) cell activity and proliferation induced by in vitro culture with interleukin-2 (IL-2) were suppressed at doses exceeding 2.5 micrograms/kg. Serum IgE levels were consistently elevated over the IL-6 dose range but IgM, IgG and IgA levels were unaffected. In summary there is a dose-dependent induction of acute-phase proteins by in vivo IL-6 treatment. At higher IL-6 doses there is a suppressive effect on NK and LAK activity measured in vitro. IL-6 may thus be useful in combination cytokine therapies that seek to suppress LAK and favour cytotoxic T lymphocyte responses. The rise in IgE levels in response to IL-6 was unexpected and suggests a more pivotal role than previously known for the control of IgE production; this could include IgE-related diseases.
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PMID:Immune function of patients receiving recombinant human interleukin-6 (IL-6) in a phase I clinical study: induction of C-reactive protein and IgE and inhibition of natural killer and lymphokine-activated killer cell activity. 830 67


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