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)

Immunoglobulin is known to be an immunomodulator. It can induce protein mediators from mononuclear cells, particularly monocytes in vitro. Intravenous immunoglobulin (IVIg) has been used as a therapy in several clinical situations. In this study, the influence of IVIg infusion on the plasma levels of two protein mediators, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), was assessed in patients with secondary generalized epilepsy. Compared to preinfusion levels, plasma interferon-gamma was increased in 18 of 18 patients 20 min after the 6- to 8-hr infusion of IVIg. Plasma interferon-gamma levels reached their peak at various times from 20 min to 3 days post IVIg infusion, dependent upon the individual patient. Plasma IL-6 levels also increased after IVIg infusion. Generally, IL-6 reached its peak level after IFN-gamma. No activated T cells or B cells were observed as determined by the expression of surface CD25, CD23, and HLA-DR 20 min following the infusion when the IFN-gamma and IL-6 levels were assessed. The expression of the high-affinity receptor for IgG, CD64, on monocytes was significantly enhanced after IVIg infusion, while the low-affinity receptor for IgG, CD32, was only slightly increased. Cytoplasmic staining of PBMC indicates that both CD16-positive and CD16-negative cells may contribute to the increase seen in plasma IFN-gamma. These data raise the possibility that the therapeutic effects of intravenous immunoglobulin may be related, at least in part, to the immunomodulatory activity as demonstrated by the changes in plasma levels of IFN-gamma and IL-6.
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PMID:Intravenous immunoglobulin induces interferon-gamma and interleukin-6 in vivo. 824 76

The expression of Fc receptors for IgG (Fc gamma R) and IgA (Fc alpha R) and of various other antigens on the human monocytic cell line U937 and peripheral blood monocytes, under stimulation with human recombinant tumour necrosis factor-alpha (TNF-alpha) and other cytokines, was investigated by flow cytometry. TNF-alpha, as well as interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) had a significant up-regulating effect on U937 expression of Fc gamma RI/CD64. Furthermore, the action of TNF-alpha was augmented by IL-6, and more evidently by IFN-gamma. IFN-alpha alone had only a marginal effect, but was able to increase the TNF-alpha-driven Fc gamma RI expression. In contrast to U937 cells, TNF-alpha did not enhance significantly Fc gamma RI expression on human monocytes. Interestingly, on both U937 cells and monocytes, Fc alpha R was augmented markedly by TNF-alpha. Furthermore, TNF-alpha induced the expression of HLA-DR and HLA-DP antigens on monocytes and U937 cells. The expression of Fc gamma RII/CD32, FC gamma RIII/CD16, CD14, complement receptor type 1 (CR1/CD35), CR4 (CD11c/CD18), and MHC class-I antigens, was not influenced significantly by TNF-alpha. The results of this study show that TNF-alpha may act on human mononuclear phagocytes, alone or in combination with other cytokines, by modulating the expression of various cell-surface antigens.
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PMID:Influence of tumour necrosis factor-alpha on the expression of Fc IgG and IgA receptors, and other markers by cultured human blood monocytes and U937 cells. 829 57

The escape of malignant cells from the immune response against the tumor may result from a defective differentiation or function of professional antigen-presenting cells (APC), ie, dendritic cells (DC). To test this hypothesis, the effect of human renal cell carcinoma cell lines (RCC) on the development of DC from CD34(+) progenitors was investigated in vitro. RCC cell lines were found to release soluble factors that inhibit the differentiation of CD34(+) cells into DC and trigger their commitment towards monocytic cells (CD14(+)CD64(+)CD1a-CD86(-)CD80(-)HLA-D Rlow) with a potent phagocytic capacity but lacking APC function. RCC CM were found to act on the two distinct subpopulations emerging in the culture at day 6 ([CD14(+)CD1a-] and [CD14(-)CD1a+]) by inhibiting the differentiation into DC of [CD14(+)CD1a-] precursors and blocking the acquisition of APC function of the [CD14(-)CD1a+] derived DC. Interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) were found to be responsible for this phenomenon: antibodies against IL-6 and M-CSF abrogated the inhibitory effects of RCC CM; and recombinant IL-6 and/or M-CSF inhibited the differentiation of DC similarly to RCC CM. The inhibition of DC differentiation by RCC CM was preceeded by an induction of M-CSF receptor (M-CSFR; CD115) and a loss of granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR; CD116) expression at the surface of CD34(+) cells, two phenomenon reversed by anti-IL-6/IL-6R and anti-M-CSF antibodies, respectively. Finally, a panel of tumor cell lines producing IL-6 and M-CSF induced similar effects. Taken together, the results suggest that the inhibition of DC development could represent a frequent mechanism by which tumor cells will escape immune recognition.
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PMID:Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. 984 45

A phase I study of escalating doses of humanized bispecific antibody (bsAb) MDX-H210 with granulocyte-colony-stimulating factor (G-CSF) was conducted in patients with metastatic breast cancer that overexpressed HER2/neu. The main objectives of the study were to define the maximal tolerated dose (MTD) of MDX-H210 when combined with G-CSF, to measure the pharmacokinetics of MDX-H210 when administered with G-CSF, and to determine the toxicity, biological effects and possible therapeutic effect of MDX-H210 with G-CSF. MDX-H210 is a F(ab)' x F(ab)' humanized bispecific murine antibody that binds to both HER2/neu and the FcgammaR1 receptor (CD64), and was administered intravenously weekly for three doses followed by a 2-week break and then three more weekly doses. A total of 23 patients were treated, and doses were escalated from 1 mg/m2 to 40 mg/m2 with no MTD reached. The toxicity of the bsAb + G-CSF combination was modest, with no dose-limiting toxicity noted: 19 patients had fevers, 7 patients had diarrhea, and 3 patients had allergic reactions that did not limit therapy. The beta-elimination half-life varied from 4 h to 8 h at doses up to 20 mg/m2. Significant release of cytokines interleukin-6, G-CSF, and tumor necrosis factor alpha was observed after administration of bsAb. Circulating monocytes disappeared within 1 h of bsAb infusion, which correlated with binding of bsAb, noted by flow-cytometric analysis. Significant levels of human anti-(bispecific antibody) were measured in the plasma of most patients by the third infusion. No objective clinical responses were seen in this group of heavily pre-treated patients.
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PMID:A phase I study of a HER2/neu bispecific antibody with granulocyte-colony-stimulating factor in patients with metastatic breast cancer that overexpresses HER2/neu. 1023 84

Monocyte phenotype, their phagocytic capacity as well as the cytokine production from 10 patients with sepsis with low interleukin-6 (IL-6) serum concentrations (<1000 pg/mL) and 8 patients with sepsis with high IL-6 (> or = 1000 pg/mL) plasma concentrations were investigated within 24 hours of fulfilling the criteria for sepsis. Monocytes from patients with high IL-6 levels had higher levels of human leukocyte antigen (HLA)-DR, HLA-ABC, CD64, and CD71, and the production of tumor necrosis factor-alpha (TNF-alpha) and IL-8, as well as the capacity of monocytes to phagocytose, was significantly elevated. Of 8 patients with high levels of plasma IL-6, 4 patients died. In contrast, all 10 patients with low plasma IL-6 concentrations survived until day 28. Patients who died had constant high IL-6 concentrations during the first 3 days, whereas IL-6 levels in patients who survived decreased by 88%. Our data indicate that IL-6 levels are a better prognostic parameter in the early phase of sepsis than the monocyte HLA-DR expression.
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PMID:Relationship between interleukin-6 plasma concentration in patients with sepsis, monocyte phenotype, monocyte phagocytic properties, and cytokine production. 1109 99

Complement plays an essential role in inflammation and tissue damage. However, it is largely unknown to what extent the system acts as a primary inducer of secondary mediator systems in the inflammatory network of human whole blood. Here we describe a novel in vitro model using the thrombin-specific hirudin analog lepirudin as anticoagulant, which, in contrast to heparin, did not interfere with complement activation. The model was used to study the role of complement in Escherichia coli-induced inflammatory responses. Granulocyte and monocyte oxidative burst was complement dependent as it was reduced by 85% and 70%, respectively, by the C3 [corrected] binding peptide compstatin. A similar reduction was found by inhibition of C5, C5a, and C5a receptor (C5aR). Furthermore, anti-CR3 antibodies were as efficient as the C5aR antagonist in reducing granulocyte oxidative burst, whereas blocking CD14 or C3aR had no effect. Up-regulation of granulocyte CR3 was virtually abolished by a C5aR antagonist. Opsonization and phagocytosis was completely inhibited by blocking of C5aR or CR3, whereas blocking of the FcgammaRs (CD16, CD32, CD64) had no effect. In contrast to oxidative burst and phagocytosis, cytokine secretion was largely complement independent. Thus, anti-CD14 abolished tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-10 secretion, whereas IL-8 was equally inhibited by anti-CD14 and compstatin. In conclusion, the present model is particularly useful for studying complement as part of the inflammatory network. The results emphasize a crucial role for C5a-C5aR interaction in E coli-induced up-regulation of CR3 and the subsequent oxidative burst and phagocytosis. Complement inhibition may have therapeutic implications in oxidative burst-induced tissue damage.
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PMID:Essential role of the C5a receptor in E coli-induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation. 1217 11

Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.
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PMID:Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. 1258 9

C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful predictor of cardiovascular events. Recent data suggest that CRP may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endothelial receptor for oxLDL that plays a pivotal role in oxLDL-induced endothelial dysfunction. Whether CRP may regulate endothelial LOX-1 and induce endothelial dysfunction through this receptor is unknown. In the present study, we studied the in vitro effect of CRP on LOX-1 expression in human aortic endothelial cells (HAECs) and the role of LOX-1 in CRP-induced human monocyte adhesion to endothelium and oxLDL uptake by endothelial cells. Incubation of HAECs with CRP enhanced, in a dose- and time-dependent manner, LOX-1 mRNA and protein levels. Induction of LOX-1 protein was already present at 5 microg/mL CRP and reached a maximum at 25 microg/mL. This effect was reduced by antibodies against CD32/CD64, endothelin-1 (ET-1) and interleukin-6 (IL-6). The extent of stimulation of LOX-1 achieved by CRP was comparable to that elicited by high glucose and IL-6 and remained unchanged in presence of these factors. Finally, CRP increased, through LOX-1, both human monocyte adhesion to endothelial cells and oxLDL uptake by these cells. We conclude that CRP enhances endothelial LOX-1 expression and propose a new mechanism by which CRP may promote endothelial dysfunction, that of inducing LOX-1.
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PMID:C-reactive protein enhances LOX-1 expression in human aortic endothelial cells: relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction. 1547 20

Diagnosis of early-onset neonatal infection has led to the development of several screening tests including C-reactive protein, a very commonly used marker, and cytokines (mainly interleukin-6 and -8), alone or in combination with C-reactive protein, based on the premise that their increases in response to infection may precede that of C-reactive protein. In recent years the search for diagnostic tests has turned to procalcitonin, a propeptide of calcitonin, which appears to be a promising marker of infection in newborn infants. Additionally, specific leukocyte cell surface antigens (mainly CD11b and CD64), detected by flow cytometry, are evaluated as markers of neonatal infection, since their expression on the cell membrane increases in substantial quantities after leukocyte activation by bacteria or their cellular products. This review aims to examine the role of these newly available immunologic indices and to assess their validity as diagnostic markers of infection during the neonatal period.
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PMID:Immunologic markers in the neonatal period: diagnostic value and accuracy in infection. 1583 52

Human embryonic stem cells (hESCs) proliferate infinitely and are pluripotent. Only a few reports, however, describe specific and efficient methods to induce hESCs to differentiate into mature blood cells. It is important to determine whether and how these cells, once generated, behave similarly with their in vivo-produced counterparts. We developed a method to induce hESCs to differentiate into mature neutrophils. Embryoid bodies were formed with bone morphogenic protein-4, stem cell factor (SCF), Flt-3 ligand (FL), interleukin-6 (IL-6)/IL-6 receptor fusion protein (FP6), and thrombopoietin (TPO). Cells derived from the embryoid bodies were cultured on a layer of irradiated OP9 cells with a combination of SCF, FL, FP6, IL-3, and TPO, which was later changed to granulocyte-colony-stimulating factor. Morphologically mature neutrophils were obtained in approximately 2 weeks with a purity and efficiency sufficient for functional analyses. The population of predominantly mature neutrophils (hESC-Neu's) showed superoxide production, phagocytosis, bactericidal activity, and chemotaxis similar to peripheral blood neutrophils from healthy subjects, although there were differences in the surface antigen expression patterns, such as decreased CD16 expression and aberrant CD64 and CD14 expression in hESC-Neu's. Thus, this is the first description of a detailed functional analysis of mature hESC-derived neutrophils.
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PMID:Derivation of functional mature neutrophils from human embryonic stem cells. 1955 31


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