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

Interleukin-6-dependent mouse hybridoma cell line KD83 was used to test the biologic activity of interleukin-6 in synovial fluid from 37 patients with temporomandibular disorders. The results showed that the interleukin-6 level was greater than 100 U/mL in 13 of 18 patients with degenerative joint disease and in five of 12 patients with temporomandibular disc displacement. However, the interleukin-6 level was less than 100 U/mL (range, 20 to 75 U/mL) in all patients with masticatory muscle disorder. It has been found that degenerative joint disease tends to have acute and chronic stages, and interleukin-6 activity was probably related to the acute stage in the patients. Histologic studies of the synovium from seven patients with degenerative joint disease showed a variable degree of hyperplasia of the synovial lining cells and chronic inflammation in five of eight specimens. Immunostaining studies clearly showed the presence of significantly more HLA-DR-expressing cells (human leukocyte antigen-D-related) in synovium. Although it is unlikely that immune responses play an important primary role in initiating synovial inflammation and cartilage destruction, immune reactions may be one important factor in the maintenance and severity of some patients with temporomandibular disorders.
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PMID:Interleukin-6 in synovial fluid and HLA-DR expression in synovium from patients with temporomandibular disorders. 748 82

Multilineage differentiation of human fetal bone marrow CD34+ cell subsets was examined using a single-cell liquid culture assay. Four CD34+ cell populations, ie, (1) CD38-, HLA-DR+, (2) CD38-, HLA-DR-, (3) CD38+, HLA-DR-, and (4) CD38+, HLA-DR+ cells, were sorted as single cells into 96-well flat-bottom culture plates containing long-term culture medium supplemented with interleukin-3, interleukin-6, stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, erythropoietin, basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1). Single CD34+, CD38-, HLA-DR+ cells had the highest replating efficiency as well as the highest replating efficiency. The cellular composition of the single-cell progeny was studied by morphologic and/or flow cytometric examination. Only the progeny of single CD34+ cells that lacked CD38 could give rise to each of the hematopoietic cell lineages. The expansion of the progeny of single CD34+, CD38-, HLA-DR+ cells was examined in more detail and showed three clearly distinguishable growth patterns: 28% (SD, +/- 10%; n = 14) of the single cells formed cell clusters/colonies; 9% (SD, +/- 4%; n = 14) formed dispersed cells; and 11% (SD, +/- 6%; n = 14) gave rise to a mixture of cell clusters and dispersed cells. The dispersed cell growth pattern was reduced when SCF or bFGF and IGF-1 was absent in the growth factor cocktail. The replating ability of the dispersed cells was considerably larger than that of cells with other growth patterns, in that 76% of the cells that gave rise to dispersed cells and 54% of the cells that gave rise to dispersed cells as well as cell clusters gave rise to a second generation, but only 7% of the cells that gave rise to cell clusters gave rise to a second generation. The second generation of cells continued to produce third and fourth generations after repetitive replating, except for the replated cells from cell clusters. In contrast with the first-generation progeny, SCF did not have an influence on the replating ability of the cells. Only in the progeny of single CD34+, CD38-, HLA-DR+ cells that gave rise to dispersed cells was each of the hematopoietic cell lineages found, ie, B lymphocytes, neutrophils, monocytes, macrophages, osteoclasts, basophils/mast cells, eosinophils, erythrocytes, megakaryocytes, and platelets.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38- hematopoietic stem cells. 751 Jan 44

We examined the role of cell adhesion molecules (CAM) by which tumor cells bind to the endothelial cells using human umbilical vein endothelial cells (HUVEC) and cultured melanoma cells. Endothelial cells from human umbilical veins were isolated and examined for CAM expression and its modulation by tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) or interferon-gamma (IFN-gamma). The expression of intercellular adhesion molecule 1 (ICAM-1) on HUVEC was increased by TNF-alpha, IL-1 and IFN-gamma when measured by ELISA or flow cytometric (FACS) analysis. IL-6 did not increase ICAM-1 expression on HUVEC. Two melanoma cell lines, Malme-3M and SK-Mel-28, showed increased expression of ICAM-1 after treatment with TNF-alpha, IL-1 and IFN-gamma in FACS analysis. IFN-gamma induced increased expression of HLA-DR only in SK-Mel-28 melanoma cells, not in Malme-3M melanoma cells. Neither HUVEC nor melanoma cells expressed lymphocyte function-associated antigen 1 (LFA-1) in either the basal (i.e., cytokine untreated) condition or the cytokine treated condition. Melanoma cells showed minimal increment in adhesion to TNF-alpha or IL-1 treated HUVEC than to cytokine untreated HUVEC. HUVEC and melanoma cells did not express LFA-1 and increased ICAM-1 expression by TNF-alpha, IL-1 and IFN-gamma treatment in FACS analysis did not coincide with minimal increase of melanoma cells adhesion to cytokine treated HUVEC. These results suggest that adhesion between melanoma cells and HUVEC is probably mediated by molecular interaction other than ICAM-1/LFA-1.
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PMID:Effect of cytokines on the expression of cell adhesion molecule and on the adhesion of melanoma cells to endothelial cells. 810 61

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

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

We studied the immunological function of hairy cells from hairy cell leukemia (HCL) patients presenting with pronounced polyclonal hypergammaglobulinemia (PPH). Hairy cell conditioned medium (HCCM) obtained from HCL patients with PPH augmented IgG production by normal peripheral blood mononuclear cells in a dose-dependent fashion, while HCCM from patients without PPH had no effect on IgG production. HCCM from the patients with PPH failed to enhance IgG synthesis by T cell-depleted mononuclear cells. Separation of T and B cells by a 0.4-microns membrane as well as monoclonal antibodies to HLA-DR and CD3 molecules prevented HCCM-dependent IgG synthesis. No B cell growth factor activity, interleukin-1, or interleukin-6 was detected in the HCCM. On examination by fractionation of the HCCM, IgG-inducing activity was detected in the fractions of 5000 to 8000 Da. These results indicate that hairy cells from HCL patients with PPH secrete a factor inducing IgG synthesis, and that the induction of IgG synthesis by the factor requires T-B cell interactions involving T cell receptor/CD3 complex and MHC class II antigens. This factor may play an important role in the development of PPH.
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PMID:Hairy cells from hairy cell leukemia patients presenting with pronounced polyclonal hypergammaglobulinemia secrete a factor enhancing IgG synthesis. 843 45

The waning of cell-mediated immunity during aging has been attributed primarily to defects in T lymphocyte properties and functions. We assessed the potential contribution of accessory dysfunction of monocytes from the elderly on responses of T cells to phytohemagglutinin (PHA) and to tetanus toxoid after in vivo boosting. Accessory function of monocytes from the elderly subjects for T lymphocyte responses to tetanus toxoid was comparable to the young. Expression of the cytokines interleukin-1, interleukin-6 and tumor necrosis factor, the cell adhesion molecules ICAM-1 and LFA-3 and the class II major histocompatibility molecule HLA-DR by monocytes from the elderly and young subjects was similar. T lymphocytes from the elderly responded poorly to PHA. Monocytes from the elderly had a decreased accessory function for PHA-stimulated T cells from young, third donors. Thus, although many accessory properties of monocytes from the elderly are normal, the monocyte and T lymphocyte defects in the elderly for mitogen may represent interactive factors in cell-mediated immunity during aging.
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PMID:Accessory function and properties of monocytes from healthy elderly humans for T lymphocyte responses to mitogen and antigen. 851 4

The production of mature monocytes/macrophages is regulated by a group of hematopoietic growth factors, or colony-stimulating factors (CSF). We investigated the in vitro effect of human hematopoietic growth factors on human blood monocyte/macrophage differentiation and proliferation in short- and long-term in vitro cultures. The addition of macrophage CSF, granulocyte-macrophage CSF, and granulocyte CSF and interleukin-6 and interleukin-3 growth factors to monocyte/macrophage cultures induced morphological changes in cultured cells, including enhancement of cell growth and the formation of multinucleated giant cells, spindle-like cells, and fibroblast-like cells. In addition, CD4 and HLA-DR antigen expression was down regulated by the addition of growth factors without a change in the expression of other surface antigens, including CD3, CD11B, CD14, CD15, NK H1, and B1. The proliferating cell nuclear antigen was not detected in growth factor-treated nonadherent monocytes/macrophages in long-term cultures. Bromodeoxyuridine was incorporated in the adherent monocytes/macrophages, and intense staining in the small rounded cells which occur above the adherent cells in these cultures was observed after a 72-h pulse, indicating that monocytes/macrophages are slowly dividing cells.
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PMID:Effect of hematopoietic growth factors on human blood monocytes/macrophages in in vitro culture. 855 11

Sclerosing pseudotumorous immune reactions of the retroperitoneum have been shown to consist of HLA-DR-positive spindle-shaped fibroblasts and macrophages that resemble fibroblasts, and in some instances they contain clonal populations of T lymphocytes not found in granulation tissue, keloids, nodular fasciitis, or fibromatoses. In patients who are iatrogenically immunosuppressed, circulating monocytes may be induced in vitro to transform into spindle-shaped macrophages, and secrete collagen after stimulation by conditioning medium from activated T lymphocytes. The authors investigated a series of five inflammatory pseudotumors (IPT) of lymph node origin for identification of spindle-shaped macrophages, T-cell receptor gene rearrangements, and lymphocyte-derived cytokine mRNA production. All cases of IPT demonstrated spindle-shaped macrophages resembling fibroblasts or myofibroblasts characterized by vimentin, CD45 (LCA), CD68 (KP1) or HAM-56, and HLA-DR(LN3) immunoreactivity and demonstrated production of procollagen-alpha1 (I) mRNA by in situ hybridization. Clonal T-cell receptor chain gene rearrangements were undetectable by polymerase chain reaction. Strong specific lymphocyte-derived interleukin-1beta and interleukin-6 mRNA cytokine transcripts were identified. Although all patients with IPT were managed with steroids and nonsteroidal anti-inflammatory medication, some had treatment-refractory disease. Because all-trans retinoic acid has been demonstrated to inhibit the in vitro transformation of monocytes into collagen-producing spindle-shaped macrophages ("neofibroblasts"), it may be of benefit for patients with IPT.
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PMID:Inflammatory pseudotumors of lymph node origin show macrophage- derived spindle cells and lymphocyte-derived cytokine transcripts without evidence of T-cell receptor gene rearrangements. Implications for pathogenesis and classification as an idiopathic retroperitoneal fibrosis-like sclerosing immune reaction. 860 85


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