Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently demonstrated that 50% of primitive human long-term culture-initiating cells (LTC-IC) are maintained for up to 8 weeks in stroma-dependent cultures in which progenitor-stroma contact is prevented (stroma noncontact), or when progenitors are cultured in medium conditioned by stromal feeders. This indicates that factors responsible for LTC-IC maintenance are present in soluble form in stromal supernatant (SN). Although the picogram concentrations of cytokines present in stromal SN can induce the differentiation of CD34+/HLA-DR- (DR-) cells to clonogenic cells (colony forming cells; CFC), they maintain only 10% of LTC-IC for 5 weeks, suggesting that factors other than these cytokines are required for LTC-IC maintenance. To characterize the factor(s) in stromal SN responsible for LTC-IC maintenance, we purified glycoproteins and proteoglycans (PG) from the SN of the LTC-IC supportive murine marrow stromal fibroblast cell line M2-10B4 by ion exchange high performance liquid chromatography (HPLC). Culture of DR- cells in a combination of M2-10B4-derived PG, but not glycoproteins and picogram concentrations of recombinant human interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), leukemia inhibitory factor (LIF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1alpha (MIP-1alpha) resulted in the recovery of 96% +/- 8% of LTC-IC maintained in cultures supplemented with unfractionated stromal SN. LTC-IC maintenance was largely retained after digestion of the PG-rich fraction with proteinase K and after dissociative gel filtration chromatography, but was completely abolished following treatment with nitrous acid, which digests heparan sulfate glycosaminoglycans (HS GAG). As for M2-10B4-derived HS GAG, high concentrations of bovine kidney HS GAG, but not bovine tracheal chondroitin sulfate, significantly improved cytokine-mediated LTC-IC maintenance. Maintenance of LTC-IC by these nonmarrow-derived HS GAG was, however, significantly lower than that seen with M2-10B4-derived HS. These studies demonstrate a role for marrow stroma-derived HS GAG in the long-term in vitro maintenance of human LTC-IC. Further structure-function analysis of these HS GAG may have important implications for ex vivo stem cell expansion and gene transfer into hematopoietic progenitors.
 ...
PMID:Stromal fibroblast heparan sulfate is required for cytokine-mediated ex vivo maintenance of human long-term culture-initiating cells. 860 38

Frozen sections of 21 gliomas were analysed to characterize inflammatory infiltrating cells, HLA-DR antigen expression and cytokine secretion. Mononuclear cells infiltrating the tumours were mostly macrophages, which were detected in 100% of cases, and expressed HLA-DR antigens. Lymphocytes were less frequently seen and expressed the CD8 phenotype. Interleukin-1 beta (IL-1 beta) and Interleukin-6 (IL-6), two cytokines mainly produced by activated cells of the macrophage lineage, were demonstrated especially in neoplastic astrocytes. IL-1 beta immunoreactivity was detected in all tumours, and was prevalent in more anaplastic gliomas; IL-6 was found in anaplastic gliomas and in glioblastomas. IL-1 receptors were expressed by both infiltrating macrophages and neoplastic astrocytes in the gliomas analysed. These findings suggest that cytokine production in gliomas seems not related to immune reactions against the tumour and their synthesis by anaplastic astrocytes could follow an unregulated activation of many metabolic processes after neoplastic transformation.
 ...
PMID:Immune infiltrates and cytokines in gliomas. 868 25

Directed migration of lymphocytes from blood into lymph nodes and organ-associated lymphatic tissue, also referred to as homing, is initiated by T-cell adhesion to specialized high endothelial cells of postcapillary vessels. Here, we demonstrate that selective signal transduction pathways specifically modulate the expression of the cutaneous lymphocyte antigen (CLA), the putative skin-homing receptor, during naive to memory transition of CD4+ T cells in vitro. The results show that the expression of CLA is strongly induced by activation via CD2 [T11.1 + T11.2 monoclonal antibodies (mAb)]. Addition of transforming growth factor-beta 1 (TGF-beta 1), interleukin-6 (IL-6), and, to a lesser extent, IL-2 further enhanced the generation of CLA+ T cells, whereas the induction of this antigen was markedly inhibited by IL-4. Periodic restimulation via CD2 and long-term culture of activated cells in the presence of IL-2 and TGF-beta 1 resulted in stable expression of CLA during a culture period of more than 100 days. In contrast, activation of naive CD4+ T cells via CD3, CD28 or by mitogens induced a rapid naive to memory phenotype transition but a much lower percentage of CLA+ T cells showing only weak expression of the antigen. Furthermore, activation of purified CD4+ memory T cells by CD2 strongly induced expression of activation-related antigens CD25 and HLA-DR, but failed to up-regulate CLA expression. Our results show that primary stimulation conditions highly modulate the development of skin-associated T cells and indicate a new functional role for costimulatory adhesion pathways in regulating the expression of molecules associated with T-cell homing.
 ...
PMID:CD2-mediated stimulation of the naive CD4+ T-cell subset promotes the development of skin-associated cutaneous lymphocyte antigen-positive memory cells. 869 Apr 52

This study was designed to investigate changes in the immune system of elite swimmers compared with well-conditioned age- and sex-matched controls in relation to a competition swim (field study). Furthermore, the aim was to reveal possible differences in immune system changes depending on the type of sport performed by comparing with an earlier study of similar design, from the same laboratory that tested elite runners in relation to a competition run. The swimmers were tested before, immediately after and 2 h and 24 h after a competition swim. Lymphocyte subsets (CD5, CD3, HLA-DR, CD4, CD8, CD19, CD3/CD16+56, CD57, CD18, CD16/CD122) all increased after the run, decreased to normal or subnormal levels after 2 h, and returned to normal after 24 h (absolute numbers). The findings were identical for the swimmers and the age- and sex-matched control group. No change in polymorphonuclear granulocyte migration was found. The lymphocyte proliferative responses decreased 2 h after the exercise. No changes were seen in plasma cytokine levels (interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in relation to exercise, but significantly lower baseline values for IL-6 were observed in the swimmers. An increase in total natural killer cell activity immediately after exercise, followed after 2 h by a decrease, was seen in both swimmers and controls. Finally, no complement activation was detected. Compared with an earlier study of elite runners, differences were seen in granulocyte chemotactic response, TNF-alpha plasma activity and the lymphocyte proliferative response to mitogen. These differences might be explained by the degree of immune system activation following muscle damage during exercise, inducing an increase in cytokines, which are known to activate and modulate both lymphocytes and granulocyte function. Our findings demonstrate identical exercise-induced, immune system changes in elite swimmers and well conditioned controls, and furthermore, the findings suggest that different types of sport performed at maximum intensity induce different immune system changes.
 ...
PMID:Short-term changes in the immune system of elite swimmers under competition conditions. Different immunomodulation induced by various types of sport. 882 44

Interleukin-6 (IL-6), a cytokine involved in the pathogenesis of sepsis and septic shock, and lymphocyte subpopulations were measured in blood circulation of patients receiving sodium nitroprusside (SNP) for induction of hypotension. The aim of this study was to evaluate whether this procedure influences distribution of lymphocyte subsets and IL-6 response. 30 patients of ASA physical status I and II scheduled for nose-septum correction were randomly assigned to the SNP- or control group (without SNP). Patients were anaesthetized with fentanyl, etomidate and isoflurane in 66% nitrous oxide. SNP was administered continuously during 60 min and mean arterial blood pressure was reduced to 50 mmHg. Before and after induction of anaesthesia, 60 min after the beginning of the operation (end of SNP-infusion) and on the first postoperative day, IL-6 plasma concentrations were determined by ELISA. The percentages of B-, T-lymphocytes, T-helper, T-suppressor cells and HLA-DR positive (activated) T-lymphocytes were examined by direct immunofluorescence using monoclonal antibodies. On the first day after surgery IL-6 plasma concentrations were significantly elevated in the SNP-group compared to preoperative values. In this group the values were higher than in control patients [30.5 (10.9-47.5) pg/ml vs. 17.4 (8.5-21.5) pg/ml]. The percentage of HLA-DR positive T-cells was 25.8 +/- 4.9% in the patients with SNP on the first postoperative day; it was significantly higher than in control patients [16.5 +/- 3.7%]. We conclude that SNP-administration increases percentage of activated T-cells and IL-6 secretion.
 ...
PMID:Increase of interleukin-6 plasma concentrations and HLA-DR positive T-lymphocytes after hypotensive anaesthesia with sodium nitroprusside. 884

Interleukin-6 (IL-6) is a cytokine with pleiotropic biologic activities on B cells, T cells, and hematopoietic progenitors. The present study was undertaken to assess pharmacodynamic effects of subcutaneous administration of IL-6 on blood counts, immunologic parameters, and acute-phase reactants. Blood samples were taken from patients with advanced renal cell cancer participating in a phase II trial of recombinant human IL-6. Multiparameter FACS analyses of peripheral blood mononuclear cells were performed using antibodies against CD3, CD4, CD8, HLA-DR, CD56, CD28, CD38, CD19, sIgM, and sIgG. Serum levels of IL-10, soluble CD23 (sCD23), sCD25, IL-1 receptor antagonist protein (IL-1RA), soluble tumor necrosis factor (TNF) receptors (sTNF-R) p55 and p75, and soluble IL-6 receptor (sIL-6R) were detected by ELISA systems. Levels of C-reactive protein (CRP), neopterin, fibrinogen, beta 2-microglobulin, and immunoglobulins M, G, and A were measured by standard methods. In response to administration of IL-6, a significant increment in platelet counts was observed, reaching peak levels after 21 days of treatment. In contrast, leukocyte subsets remained unaffected. No change in number of immunophenotype of peripheral blood B cells, T cells, or natural killer cells could be detected following IL-6 administration. Blood levels of sCD23, IL-10, sIL-6R, neopterin, beta 2-microglobulin, and immunoglobulin subsets were not influenced by cytokine therapy. However, administration of IL-6 led to a slow increment of acute-phase reactants CRP and fibrinogen. Furthermore, the anti-inflammatory molecules sTNF-R p55 and p75 were induced by IL-6, whereas serum levels of IL-1RA remained unchanged. Finally, an increase in blood levels of sCD25 was observed. In conclusion, IL-6 in vivo predominantly acts as a regulator of inflammation and a megakaryocyte differentiation factor.
 ...
PMID:Immunomodulatory and hematopoietic effects of recombinant human interleukin-6 in patients with advanced renal cell cancer. 893 65

By using a double-label immunohistochemistry technique, we demonstrated the presence of interleukin-6 (IL-6) in acute and chronic active plaques from the brain of six patients with multiple sclerosis (MS). IL-6 was mainly associated with astrocytes and rarely with macrophages or mononuclear infiltrating cells. The pattern of distribution for IL-6 immunoreactivity was similar to that of HLA-DR expression, but the two molecules almost never colocalized on the same cell. Our data indicate that in MS central nervous system IL-6 is predominantly located within resident glial cells which are concentrated at the sites of ongoing demyelination and immune activation. Although IL-6 exhibits several proinflammatory activities, indirect evidence suggests that the cytokine may also play an immunomodulatory role in inflammatory demyelinating disorders.
 ...
PMID:IL-6 detection in multiple sclerosis brain. 907 97

CD4 and CD8 T lymphocyte subsets, the late T cell activation marker, HLA-DR, and serum interleukin-6 (IL-6) levels of 57 polymyalgia rheumatica (PMR) patients were followed over 2 yr to investigate whether they could be used to predict the safe withdrawal of steroid therapy. Cell phenotypes were studied by flow cytometry and IL-6 levels by ELISA. %CD8 cells were reduced below the normal range in PMR patients prior to steroid therapy. In 56% of patients, the %CD8 T lymphocytes failed to return to normal levels when quiescent disease allowed cessation of steroid therapy. Activated CD8 T cells, as detected by HLA-DR positivity, were above the normal range at the initiation of therapy and showed a negative correlation with %CD8 T cells. The serum concentration of IL-6 fluctuated over 24 months, and the correlation between IL-6 and erythrocyte sedimentation rate (ESR) seen prior to treatment was not seen at later intervals. The %CD8 T cell and serum IL-6 levels are not a good indicator of disease activity in PMR and are, therefore, unable to predict the safe withdrawal of steroids.
 ...
PMID:The sequential analysis of T lymphocyte subsets and interleukin-6 in polymyalgia rheumatica patients as predictors of disease remission and steroid withdrawal. 937 94

A whole-blood model was used to evaluate the effects of temperature and anticoagulant on the expression of activation markers HLA-DR and CD11b on peripheral leukocytes. Venous blood, anticoagulated with either EDTA or heparin, was obtained from six healthy blood donors and 13 hospitalized patients (8 human immunodeficiency virus type 1-seropositive individuals with concurrent pulmonary tuberculosis and 5 patients with pneumonia). A preliminary evaluation was carried out with whole blood from two of the normal donors, and cells were stained immediately for HLA-DR and CD11b markers or stained after incubation at room temperature or 37 degreesC for 18 h with or without the addition of the cytokines gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma plus GM-CSF, tumor necrosis factor beta, or interleukin-6. Of the cytokines tested, the combination of IFN-gamma and GM-CSF had the most pronounced modulation of marker expression on polymorphonuclear neutrophils (PMN), in particular, HLA-DR expression, which required induction for its detection. These cytokines were therefore used in further evaluations that considered the above-mentioned effects in the presence of disease. Results indicated that the expression of activation markers on PMN and lymphocytes in whole blood are influenced by the temperature of incubation and the choice of anticoagulant and the effects noted were dependent on (i) the particular cell surface marker, (ii) the cell type being studied, and (iii) the presence or absence of disease. It is therefore recommended that ex vivo whole-blood models for evaluating phenotype or immune function be carefully evaluated for the above-mentioned effects.
 ...
PMID:Effects of anticoagulants and temperature on expression of activation markers CD11b and HLA-DR on human leukocytes. 972 38

The monocyte/macrophage (Mphi is central in the regulation of the immune response in states of trauma and sepsis. Because monocyte subsets, characterized by expression of the Fc-receptor (FcR), were shown to play distinct immunologic roles in trauma, it was the objective of this study to assess insights into the functional role of FcR positive (FcR+) and negative (FcR-) subclasses in surgical sepsis. In a prospective study, peripheral blood Mphi from 20 septic patients and 10 healthy volunteers were evaluated on consecutive days after the onset of sepsis. FcR+/- subsets were separated by rosetting with antibody-coated human erythrocytes. Receptor expression and synthesis of proinflammatory cytokines were used to evaluate the functional role of these cells. We demonstrated a significant monocytosis (350%; p<.01) and suppression of human lymphocyte antigen (HLA-DR) expression (35%; p<.05). Synthesis of Interleukin-1beta (IL-1beta; e.g., Day 1: 230+/-30 pg/mL) and Interleukin-6 (IL-6; e.g., Day 1: 1920+/-350 U/mL) were significantly higher (p<.05) in FcR+ subsets than in controls (IL-1beta: 100+/-5 pg/mL; IL-6: 353+/-75 U/mL). Tumor necrosis factor-alpha (TNF-alpha) was elevated in FcR+ monocytes but did not reach a significant value. Interleukin-8 (IL-8) synthesis showed only on Day 1 and in controls significant differences in FcR+ and FcR- cells (Day1: FcR-: 19.6+/-4.1 nM; FcR+: 9+/-4.3 nM). Sepsis results in a significant shift toward FcR+ monocytes. This cell population is characterized by high proinflammatory cytokine synthesis. The extent of this shift seems to identify a group of high risk septic patients that might benefit from immunomodulatory therapy.
 ...
PMID:Evaluation of Fc-receptor positive (FcR+) and negative (FcR-) monocyte subsets in sepsis. 1022 Feb 97


<< Previous 1 2 3 4 5 6 7 Next >>