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)

Our present study was designed to clarify the mechanism by which the same megakaryocyte progenitor cells respond to various cytokines at different stages of megakaryocyte development. We examined the changes in mRNA expression of granulocyte macrophage colony-stimulating factor receptor beta-subunit (GM-CSFR beta-subunit), which was a common subunit of a high-affinity interleukin-3 receptor (IL-3R) and a high-affinity GM-CSFR, and interleukin-6 receptor (IL-6R) during megakaryocyte development in a human megakaryocytic leukemia cell line (CMK) which could proliferate and/or differentiate in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, GM-CSF, and IL-6. We found that GM-CSFR beta-subunit mRNA was expressed constitutively in CMK cells and was transiently down-regulated by TPA and IL-6, while the expression of IL-6R mRNA was increased by TPA in association with the differentiation of megakaryocytes. Furthermore, the TPA-induced down-regulation of GM-CSFR beta-subunit mRNA expression and its recovery were blocked by cycloheximide (CHX), a protein synthesis inhibitor, suggesting that these modulations required de novo protein synthesis. These findings imply that multi-lineage cytokines such as GM-CSF and IL-3 may contribute preferentially to the regulation of the earlier development of megakaryocyte progenitor cells with high densities of multi-lineage cytokine receptors, while IL-6 may be limited in its action to supporting the maturation of more differentiated megakaryocyte progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Leuk Lymphoma 1992 Nov
PMID:Modulation of GM-CSF receptor beta-subunit and interleukin-6 receptor mRNA expression in a human megakaryocytic leukemia cell line. 129 Sep 64

The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large-cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.
 ...
PMID:Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients. 132 Sep 56

Ki-1-positive large cell anaplastic lymphoma (Ki-1 LCAL) is recognized as a clinicopathologic syndrome with fever, peripheral lymphadenopathy and cutaneous nodules; the neoplastic cells express Hodgkin's disease-associated antigen, Ki-1 (CD30). We review here a recent case of Ki-1 LCAL with multiple bone lesions with destruction and present additional information. Although bone absorption is reported in some cases of Ki-1 LCAL, the genesis of bone absorption is unclear. Interleukin-6 (IL-6) is an important regulator of osteoclast formation and activation and can induce bone absorption. In our case, the surgically removed tumor tissue was studied for IL-6 mRNA expression and IL-6 secretion without any stimulation. Northern blot analysis showed strong IL-6 mRNA expression in the tumor tissue and ELISA assay showed a large amount of IL-6 in culture supernatants of the tumor tissue. Based on these results, coupled with the reported evidence, we discuss the close relationship between the presence of osteolytic lesions and IL-6 production in Ki-1 LCAL.
Leuk Lymphoma 1992 Jul
PMID:Ki-1 positive large cell anaplastic lymphoma: multiple bone lytic lesions and interleukin-6. 133 92

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells. IL-4 and IL-6 increased significantly EBV-B cell proliferation after 3 and 5 days of culture, where IL-2 had no effect. The effect of IL-4 and IL-6 on EBV-B cells was abolished after pre-incubation with anti-IL-4 and anti-IL-6 neutralising antisera, respectively. TPA induced a dose dependent inhibition of proliferation both in serum free and 10% fetal calf serum (FCS) supplemented culture medium. Combinations of TPA and interleukins did not restore lymphoblastoid cell proliferation to background levels. All possible combinations of the three cytokines showed no synergistic or antagonistic effect on proliferation. TPA induced significant phenotypic changes of EBV immortalised B lymphocytes, by increasing IL-2 receptor (IL-2R) expression and decreasing CD20 and CD23 antigen expression. Other B cell differentiation antigens; HLA-DR, CD19, and transferrin receptor (CD71), did not demonstrate significant changes. A dose dependent inhibition of CD21 and increase in CD22 expression was observed in 2 out of 3 lymphoblastoid cell lines tested.
Leuk Lymphoma 1992 Sep
PMID:Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes. 133 96

Cerebrospinal fluid (CSF) and serum samples of 20 patients with central nervous system manifestations of hematological malignancies including primary cerebral lymphoma (n = 5) and disseminated non-Hodgkin lymphoma (n = 7) were examined for albumin, IgG, IgM, fibronectin, beta 2-microglobulin, interleukin-6, soluble interleukin-2 receptor, tumor necrosis factor alpha, and oligoclonal immunoglobulin bands. Although a broad range of abnormalities were detected, no reliable CSF parameter for the diagnosis of leptomeningeal spread from hematological neoplasias could be identified. An analysis of 61 repeat lumbar punctures added little to the findings of the first CSF examinations. Currently, immunochemical studies of CSF cell surface markers and early biopsy have probably more clinical value than the determination of the humoral CSF parameters included in this study. However, analysis of cytokine synthesis by single CSF cells using molecular biology techniques may improve the differential diagnosis of hematological neoplasia of the brain and spinal cord in the future.
 ...
PMID:Humoral CSF parameters in the differential diagnosis of hematologic CNS neoplasia. 141 21

A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki-67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi]-negative), different from that of normal plasma cells (IL-6-negative/GST-pi-positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non-Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL.
 ...
PMID:Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas. 141 84

Interleukin-6 (IL-6) has been shown to increase platelet counts in several animal models and to enhance megakaryocytopoiesis in vitro. In order to investigate the possible relationship between IL-6 and thrombocytosis, serum IL-6 levels in patients with platelet counts > or = 6 x 10(5)/microliters were measured using an IL-6-responsive bioassay. A cohort of healthy volunteers with normal platelet counts was used to establish a control mean serum IL-6 level [2.19 U/ml +/- 1.08 SD (range 0-5.5)]. Patients with primary thrombocytosis had a mean serum IL-6 level not significantly different from controls. In comparison, serum IL-6 levels of patients with reactive thrombocytosis were significantly greater than controls (38.3 U/ml +/- 94.6; range 0-933; P < 0.001). Although no significant correlation was observed between the degree of serum IL-6 elevation and the height of the platelet count in any individual, elevated serum IL-6 was highly correlated with reactive thrombocytosis.
Leuk Lymphoma 1992 Oct
PMID:Serum interleukin-6 levels in patients with thrombocytosis. 149 Jan 50

Interleukin-6 (IL-6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL-6 (S-IL-6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S-IL-6 levels in 102 patients with monoclonal gammopathy (MG). S-IL-6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti-IL-6 antibody and a human recombinant IL-6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within-run and between-run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL-6 standard and S-IL-6 was shown by dilution tests. IL-6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S-IL-6 values were 294 +/- 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S-IL-6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S-IL-6 levels correlated with bone-marrow plasmacytosis (P less than .0005), serum-lactate dehydrogenase (S-LDH; P less than .005), serum beta 2 microglobulin (S -beta 2m; P less than .01), and serum calcium (S-Ca; P less than .025) and inversely correlated with haemoglobin (P less than .025). Our results indicate that 1) radioimmunoassay is suitable for the measurement of human IL-6 in serum; 2) high S-IL-6 levels are observed in a small number of patients with MG; and 3) S-IL-6 level correlates with tumour cell mass in patients with overt MM.
 ...
PMID:Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma. 154 13

Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Experimental evidence supporting the usefulness of ursodeoxycholic acid as a potentially beneficial therapeutic agent for primary biliary cirrhosis has been reported from the biochemical and physiological aspects. In this study, we investigated the direct effects of ursodeoxycholic acid on immunoglobulin and cytokine production in vitro using plaque-forming cell assay and enzyme-linked immunosorbent assay. It was demonstrated that ursodeoxycholic acid suppressed the production of IgM, IgG and IgA induced by Staphylococcus aureus Cowan I in peripheral blood mononuclear cells derived from healthy subjects and patients with primary biliary cirrhosis and also in human B lymphoma cell lines. Furthermore, ursodeoxycholic acid suppressed interleukin-2 and interleukin-4 production induced by concanavalin A and interferon-gamma production induced by polyinosinic-polycytidylic acid, but it did not affect interleukin-1 and interleukin-6 production induced by lipopolysaccharide in peripheral blood mononuclear cells. In addition, ursodeoxycholic acid suppressed the concanavalin A-induced thymocyte proliferation mediated by interleukin-1. Cytotoxicity against lymphocytes was not observed at the concentrations of ursodeoxycholic acid used. These results suggest that the beneficial effect of ursodeoxycholic acid in primary biliary cirrhosis is mediated in part by immunosuppression.
 ...
PMID:Immunomodulatory effects of ursodeoxycholic acid on immune responses. 163 44

The 'Workshop on Growth Factors' which took place at the Lugano Lymphoma Conference on June 8, 1990, included a presentation by Michael Sporn on the concept that loss of inhibitory control mechanisms may be important in the development and growth of human cancer. Examples illustrating this were taken from current experimental biology research into transforming growth factor beta (TGF-beta) interactions. Brian Durie presented recent data on the biology of interleukin-6 (IL-6) and its putative role in plasma cell diseases. These studies have culminated in the first clinical study of the role of an antibody to a growth factor as therapy for a human cancer (anti-IL-6 antibody as therapy for patients with myeloma). Derek Crowther presented data concerning the current clinical role of the haematopoietic growth factors in patients undergoing chemotherapy for cancer. Recent clinical research has established the role of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in improving the safety of high-dose or accelerated chemotherapy, and their use is associated with enhanced neutrophil recovery following ablative therapy and bone marrow rescue. This session was followed by the presentation of three papers concerning the use of G-CSF and GM-CSF in association with chemotherapy for patients with malignant lymphoma.
 ...
PMID:Workshop on growth factors. 167 82


1 2 3 4 5 6 7 8 9 10 Next >>