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)

It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. this review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-t (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-gamma and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-alpha, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-gamma and IL-2 production as well as TNF-beta. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.
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PMID:Cytokine production pathway in the elderly. 873 67

We established a system of receptor chimeras that enabled us to induce heterodimerization of different cytoplasmic tails. Fusion constructs were created that are composed of the extracellular parts of the interleukin-5 receptor alpha and beta chains, respectively, and the transmembrane and intracellular parts of gp130, the signal transducing chain of the interleukin-6 receptor complex. In COS-7 transfectants we observed a dose-dependent interleukin-5-inducible STAT1 activation for which the presence of both the alpha and the beta chain chimera was needed. No STAT activity was detected if one of the cytoplasmic tails of the receptor complex was deleted, indicating that STAT activity resulted from a receptor dimer rather than from higher receptor aggregates. We further investigated whether dimerization of STAT1 depends on the juxtaposition of two STAT recruitment modules in a receptor complex. We show that a receptor dimer with only a single STAT1 docking site was still able to lead to STAT1 activation. This indicates that the formation of a paired set of STAT binding sites in a receptor complex is not the prerequisite for STAT factor dimerization. Our findings are discussed in view of alternative STAT dimerization models.
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PMID:A single STAT recruitment module in a chimeric cytokine receptor complex is sufficient for STAT activation. 903 May 99

We have previously proposed that pro-inflammatory cytokines and nitric oxide (NO) contributed to reversible myocardial depression in patients with sepsis and congestive heart failure. Sepsis and heart failure are also associated with refractoriness to beta-adrenoceptor agonists. Therefore, the chronotropic effects of cytokines and the NO synthase inhibitor, NG-methyl-L-arginine (NMA), on beta-adrenoceptor stimulation of neonatal cardiac myocytes were studied. Tumor necrosis factor alpha, interleukin-1 beta and interleukin-6 but not interleukin-4 or interleukin-5 significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 h (P < 0.01; n = 12 for each). NMA also significantly enhanced spontaneous beating rates (P < 0.01; n = 12 for each). Only interleukin-1 beta treatment resulted in significant nitrite production, immunohistochemical staining for inducible nitric oxide synthase and detection of inducible NO synthase messenger RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). However, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and NMA each completely blocked the positive chronotropic effects of the beta-adrenoceptor agonist, isoproterenol (P < 0.01; n = 12 for each). These findings are most consistent with an inducible NO synthase-independent effect of cytokines and NMA on the chronotropic responses of neonatal cardiac myocytes to beta-adrenoceptor stimulation. This effect of cytokines and NMA on adrenergic signaling may involve a myocardial constitutive NO synthase or an NO-independent mechanism.
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PMID:Cytokines and nitric oxide synthase inhibitor as mediators of adrenergic refractoriness in cardiac myocytes. 905 50

Enteric infection of mice with respiratory enteric orphan virus (reovirus) type 1, strain Lang elicits both humoral and cellular immune responses. To investigate the role of CD8+, alpha/beta T-cell receptor (TCR)+ T cells in mucosal immunity to an enteric pathogen, we examined immune responses and viral clearance following enteric reovirus infection in C57BL/6, B6129F2, and beta2-microglobulin-deficient (beta2m-/-) mice. Analysis of Peyer's patch and lamina propria culture supernatants revealed a two- to threefold increase in levels of reovirus-specific immunoglobulin A in beta2m-/- mice compared to normal controls. These data corresponded to a similar increase in the frequency of virus-specific immunoglobulin A-producing cells in Peyer's patches and lamina propria and an increase in immunoglobulin G-producing cells in spleens from beta2m-/- mice compared to controls. These increased humoral immune responses were not due to a difference in B-cell populations because cell counts and flow cytometric analyses showed that beta2m-/- and control mice had similar numbers and percentages of B cells in mucosal and systemic tissues. Analysis of cytokine message by reverse transcriptase-PCR 5 and 10 days after infection revealed no difference in message level for transforming growth factor beta, gamma interferon, interleukin-4, interleukin-5, or interleukin-6 for all mouse strains. Virus tissue titers determined by plaque assay at 5 and 10 days after infection demonstrated that beta2m-/- mice cleared reovirus from the small intestines with the same efficiency as control mice. Collectively, these data suggest that CD8+, alpha/beta TCR+ T cells may regulate mucosal and systemic humoral immune responses to oral infection with reovirus.
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PMID:Enhanced mucosal and systemic immune responses to intestinal reovirus infection in beta2-microglobulin-deficient mice. 922 66

When used in commercial fermented dairy products, bifidobacteria may enhance immunity by stimulating cytokine secretion by leukocytes. To assess whether interaction between bifidobacteria and leukocytes promote cytokine production, we cultured RAW 264.7 cells (macrophage model) and EL-4.IL-2 thymoma cells (helper T-cell model) in the presence of 14 representative strains of heat-killed bifidobacteria. In unstimulated RAW 264.7 cells, all bifidobacteria induced pronounced increases (up to several hundred-fold) in the production of tumor necrosis factor-alpha compared with that of controls. Interleukin-6 production by unstimulated cells also increased significantly, but less than did tumor necrosis factor-alpha. Upon concurrent stimulation of RAW 264.7 cells with lipopolysaccharide, production of tumor necrosis factor-alpha and interleukin-6 were both enhanced between 1.5- to 5.8-fold and 4.7- to 7.9-fold, respectively, when cultured with 10(8) bifidobacteria/ml. In unstimulated EL-4.IL-2 cells, bifidobacteria had no effect on the production of interleukin-2 or interleukin-5. Upon stimulation of EL-4.IL-2 with phorbol-12-myristate-13-acetate, there were variable increases in interleukin-2 secretion (up to 2.4-fold for 10(6) Bifidobacterium Bf-1/ml) and interleukin-5 secretion (up to 4.6-fold for 10(8) B. adolescentis M101-4). The results indicated that, even when variations among strains were considered, direct interaction of most bifidobacteria with macrophages enhanced cytokine production, but the effects on cytokine production by the T-cell model were less marked. Interestingly, the 4 bifidobacteria strains used commercially for diary foods showed the greatest capacity for cytokine stimulation. The in vitro approaches employed here should be useful in future characterization of the effects of bifidobacteria on gastrointestinal and systemic immunity.
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PMID:Differential cytokine production in clonal macrophage and T-cell lines cultured with bifidobacteria. 940 65

We investigated the effect of oral feeding of heat-killed Lactobacillus casei strain Shirota on immunoglobulin E (IgE) production in mice. The strain was orally administered to BALB/c mice that had been preinjected intraperitoneally with ovalbumin, and the level of IgE in serum was determined. Results indicated that the oral feeding of L. casei strain Shirota was effective in inhibiting IgE production in serum, and the IgE production in response to ovalbumin was significantly inhibited in the mice. The in vitro production of IgE by the spleen cells from mice fed L. casei strain Shirota in response to restimulation with ovalbumin was inhibited in contrast to that of spleen cells from the control group. We also examined the pattern of cytokine production by spleen cells from mice fed L. casei strain Shirota followed by restimulation with ovalbumin in vitro. In the mice fed L. casei strain Shirota, the production by the spleen cells of Th1 cell-associated cytokines, such as interferon-gamma and interleukin-2, was higher than that by the spleen cells from the control group. In contrast, the production of Th2 cell-associated cytokines, such as interleukin-4, interleukin-5, interleukin-6, and interleukin-10, by spleen cells in the group fed L. casei strain Shirota was lower than that by the cells from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed L. casei strain Shirota was also higher than that of the control group.
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PMID:The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice. 949 81

Eosinophils, prominent cells in asthmatic inflammation, have been shown to synthesize, store, and release an array of up to 18 cytokines and growth factors, including interleukin-6 (IL-6). In this report, we show that IL-6 immunofluorescence localizes to the matrix of the crystalloid granule in peripheral blood eosinophils from atopic asthmatics using confocal laser scanning microscopy (CLSM). Granule localization of IL-6 was confirmed using dot-blot analysis and enzyme-linked immunosorbent assay (ELISA) on subcellular fractions of highly purified eosinophils produced from density centrifugation across a 0% to 45% Nycodenz gradient. IL-6 was found to coelute with eosinophil crystalloid granule marker proteins, including eosinophil peroxidase (EPO), major basic protein (MBP), arylsulfatase B, and beta-hexosaminidase. Immunoreactivity to IL-6 colocalized with granule-associated IL-2 and IL-5 in subfractionated eosinophils. We also made the novel and compelling observation that interferon gamma (IFNgamma), a Th1-type cytokine, stimulated an early elevation in eosinophil IL-6 immunoreactivity. A 2.5-fold enhancement of IL-6 immunoreactivity in eosinophil granules was observed within 10 minutes of IFNgamma treatment (500 U/mL), as determined by subcellular fractionation and CLSM. These findings suggest that IFNgamma has short-term effects on human eosinophil function and imply that a physiologic role exists for Th1-type cytokine modulation of Th2-type responses in these cells.
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PMID:Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics and effects of interferon gamma. 951 52

The potential contribution made by the inflammatory cytokines, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) to the adjuvant activity of aluminium hydroxide gels (Alum) or Freund's complete adjuvant (FCA) was studied by comparing the immunological responses of IL-6- or TNF receptor 1- (p55; TNFR-1) deficient mice with immunocompetent control mice. While both TNFR-1- and IL-6-deficient mice primed with ovalbumin (OVA) prepared in either Alum or FCA produced similar IgG.1 responses in comparison to control mice, the pattern of T-helper type 1- (Th1) dependent IgG2a production was significantly altered. In TNFR-1-deficient mice, IgG2a responses were greater than in control mice when FCA, but not when Alum, was used as an adjuvant. Correspondingly, spleen cells from FCA-inoculated TNFR-1-deficient mice restimulated with antigen in vitro produced higher Th1 cytokine (interferon-gamma; IFN-gamma) levels with no alteration in Th2 cytokine (IL-4; IL-5, IL-6 and IL-10) production in comparison with wild-type mice. Higher levels of IgG2a were also detected in IL-6-deficient mice compared with wild-type mice following inoculation with OVA prepared in either FCA or in Alum. Furthermore, analysis of cytokine production by spleen cells revealed that both Th1 and Th2 cytokine production was higher in IL-6-deficient mice compared with control mice. As the majority of the effects of TNF-alpha are mediated via TNFR-1, we conclude that this cytokine inhibits the adjuvant activities of FCA. Furthermore, the results also imply that immunopotentiating effects of FCA or Alum adjuvant are both inhibited by IL-6.
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PMID:Neither interleukin-6 nor signalling via tumour necrosis factor receptor-1 contribute to the adjuvant activity of Alum and Freund's adjuvant. 953 17

Seeds from Acalypha wilkesiana (Euphorbiaceae) are an essential component of a complex plant mixture used empirically by traditional healers in Southwest Nigeria to treat breast tumours and inflammation. To investigate their biological properties, we incubated human lymphocytes and granulocytes with aqueous and ethanolic extracts of A. wilkesiana seeds (AWS). In lymphocytes, we observed an induction of apoptosis and generation of reactive oxygen intermediates (ROI), as measured by the oxidation of hydroethidine, within 2 h, while in granulocytes, an aqueous seed extract induced the oxidative burst and enhanced phagocytosis of Escherichia coli within 10-20 min. In the supernatants of 72-h cultured lymphocytes, AWS induced the release of the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and also T-cell-associated cytokines interleukin-5 and interferon-gamma. These preliminary results encourage further investigations of this drug with both cytotoxic and immunomodulating properties.
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PMID:Apoptosis-associated generation of reactive oxygen intermediates and release of pro-inflammatory cytokines in human lymphocytes and granulocytes by extracts from the seeds of Acalypha wilkesiana. 1047 77

Increasing evidence suggests that the pattern of T-cell cytokine production can be modulated by antigen presenting cell (APC)-derived factors during the cell interactions. Recently, it has been shown that alveolar macrophages (AMs) from atopic asthmatics (AA) but not atopic nonasthmatics (AN) enhance interleukin (IL)-5 production by CD4+ T-cells. The present study compared AM production of IL-1beta, IL-6, and IL-12, as well as their associated functional capacity to influence IL-5 production by allergen-specific CD4+ T-cells in 10 AA, 10 AN, and nine nonatopic control subjects (C). AMs from AA showed a relatively high production of IL-1beta and IL-6 (p<0.05) and a relatively low secretion of IL-12 compared to C, whereas AMs from AN and C behaved similarly. This study confirmed previous findings that co-culture with AMs augments IL-5 production from allergen-stimulated CD4+ T-cells only in AA and not in nonasthmatics even if they are atopic. On the other hand, stimulation with allergen alone did not enhance IL-5 production by CD4+ T-cells in either AA nor AN. AM-induced changes in CD4+ T-cell IL-5 production upon allergen stimulation significantly correlated with their ability to produce IL-1beta (r=0.59, p<0.01), IL-6 (r=0.56, p<0.01), and inversely with IL-12 (r=-64, p=0.002) in all atopic subjects, and even more closely with the ratio of IL-12/IL-1beta (r=-0.75, p<0.001) and IL-12/IL-6 production (r=-0.81, p<0.001) in these subjects. These findings suggest that the role of alveolar macrophages from atopic asthmatics in enhancing interleukin-5 production by allergen-specific CD4+ T-cells is due, at least partly, to their aberrant production of interleukin-1beta, interleukin-6, and particularly of interleukin-12.
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PMID:Modulatory effects of alveolar macrophages on CD4+ T-cell IL-5 responses correlate with IL-1beta, IL-6, and IL-12 production. 1048 36


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