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)

Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).
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PMID:Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas. 128 90

We examined cerebrospinal fluid (CSF) samples from 12 patients with SLE and active central nervous system (CNS) involvement for their levels of the following cytokines: interleukin-1 (IL-1) by means of two different assays--the IL-1 responsive murine cell line LBRM 33-la5 and an ELISA for IL-1 alpha; IL-2 by means of the CTLL cell line responsive to it; and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) both determined by a specific ELISA. We found that SLE CSF had significantly higher levels of IL-1 and IL-6 than did those obtained at surgery from eight controls without inflammatory neurologic disease. IL-2 and TNF were not detectable in any of the CSF samples. We also studied the status of activation in CSF T cells using monoclonal antibodies against early (anti-IL-2R (CD25) and anti-transferrin (CD71)), late (anti-T10) and very late (anti-VLA-1) activation antigens, and found increased percentages of T10-bearing (18 +/- 2 vs 3 +/- 0.7%) and VLA-1-bearing T cells (12 +/- 2 vs 0.7 +/- 0.2%) in SLE patients as compared to controls (both P < 0.01). Levels of IL-1 and IL-6 correlated with T10 and those of IL-1 correlated also with VLA-1. Markers of early T-cell activation did not differ in SLE and control CSF. Because of these findings we analysed the effect of recombinant IL-1, IL-6 or normal CSF on normal T cells and found that they did not induce the expression of activation markers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers. 130 62

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.
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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

The aim of this study was to establish a cytokine-free, serum-free system which would enable the long-term survival and proliferation of human peripheral blood monocytes. Monocytes were isolated from peripheral blood mononuclear cells (PBMC) by adherence to untreated plastic petri dishes and maintained up to 6 weeks in serum-free medium (SFM) consisting of IMEM, insulin, transferrin, sodium selenite and BSA. Maximal cell proliferation occurred during the first 2 weeks of culture and corresponded to the appearance of large numbers of pure, nonadherent culture-derived macrophages. Monocyte maturation was characterised by the modulation of specific cell surface antigens. The percentage of cells staining for the transferrin receptor increased with time, whereas the percentages of cells expressing CD11b, CD11c and HLA-DR remained greater than 60% for the 15 days studied. The mean fluorescent intensities (MFI) of all these antibodies increased significantly with time. The only differences found between the adherent and nonadherent cells, using the above antibodies, were with the MFI for CD11b and CD11c. In both cases, the intensity of staining was significantly greater in the adherent cells. Estimation of cytokine production by cells maintained for 5 weeks in SFM found that they constitutively produced large amounts of macrophage colony-stimulating factor (M-CSF) in the absence of any exogenous stimuli. These cells were also found to secrete high levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) during the 1st week and granulocyte macrophage colony-stimulating factor (GM-CSF) during the 3rd week. However, the addition of exogenous GM-CSF (5 U/ml, S5) was found to significantly inhibit monocyte proliferation up to 17 days. This is the first report of proliferation associated with long-term survival of culture derived macrophages in a serum-free, cytokine-free system.
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PMID:Monocyte proliferation in a cytokine-free, serum-free system. 151 90

Transferrin receptor expression is vital for the continuous growth of most cells. Although iron plays a key role in modulating transferrin receptor expression, other physiological factors are also capable of affecting receptor expression. In hematopoietic cells, these include interleukin-2, interleukin-6, calcium channels, cyclic nucleotides, phorbol esters and viruses. In this review, we will describe how these agents can alter transferrin receptor expression at the levels of transcription, translation and receptor re-cycling.
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PMID:Regulation of transferrin receptor expression and control of cell growth. 164 75

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.
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PMID:Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy. 170 43

The murine B-cell hybridoma B9 requires interleukin-6 (IL-6) for its survival and proliferation in vitro. We show here that withdrawal of IL-6 from B9 cultures results in programmed death, concomitant with arrest of the cells in the G1 phase of the cell cycle. Unlike several other systems that undergo programmed cell death, no induction of transcripts corresponding to the testosterone-repressed message-2 or transglutaminase genes is observed during this process. Upon readdition of IL-6 to G1-arrested B9 cells, viability is maintained and entry into S phase occurs after a lag period of 10 to 12 hr. Northern blot analysis showed that the immediate-early mRNAs normally induced shortly after growth factor stimulation in quiescent fibroblasts (c-fos, c-jun, Egr-1, c-myc, JE, and KC), and other growth-related genes (2F1, c-Ha-ras, and p53), are either not induced or remain unchanged during G1 to S phase progression. A correlation was found, however, between the temporal pattern of expression of several G1/S phase genes (dihydrofolate reductase, thymidine kinase, transferrin receptor, and histone H3) and DNA synthesis. These results demonstrate that IL-6-induced viability and growth of hybridoma (and, presumably, plasmacytoma) cells is mediated via novel signal transduction pathways.
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PMID:Suppression of programmed death and G1 arrest in B-cell hybridomas by interleukin-6 is not accompanied by altered expression of immediate early response genes. 170 72

The humoral antibody immunodeficiency in two patients with T-cell chronic lymphocytic leukemia (T-CLL) appeared to be the result of immunoregulatory abnormalities in the leukemic T-cell populations. Both patients had CD4+ CD45R+ "virgin" or suppressor-inducer T-CLL, but Patient 1 had hypogammaglobulinemia and Patient 2, immunoglobulin (Ig) M hypergammaglobulinemia. Although, CD25+ interleukin-2 (IL-2) receptors were present on leukemic T-cells of both patient, OKT9+ (CD71) transferrin receptors and OKT10 (CD38) activation antigens were found only on Patient 2's cells. Highly elevated amounts of IL-2 was secreted from phytohemagglutinin-stimulated and concanavalin A-stimulated T-cells in both patients. In Patient 1 with hypogammaglobulinemia, immune defects involve T-cells, first an intense suppressor activity on B-cell-induced IgM and IgG synthesis and, second, deficient production of B-cell growth factor (BCGF) and B-cell differentiation factor (BCDF). In Patient 2, highly elevated BCGF and IgM-specific BCDF was secreted by T-cells, a mechanism leading to IgM hypergammaglobulinemia in this patient. These studies stress the importance of BCGF and BCDF activity of leukemic T-cells in humoral antibody immunodeficiency disorders in T-CLL cases.
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PMID:Humoral immunodeficiency in T-cell chronic lymphocytic leukemia. An immunologic assessment. 201 51

Immunocompetent cells communicate via direct cellular contact and/or by the release and binding of soluble mediators. These soluble mediators transmit signals for growth and differentiation of various cell types. We have been intensively studying the regulation of human B lymphocytes and have focused on the events which occur following stimulation of mature, resting B cells with antigen or an antigen equivalent, anti-immunoglobulin antibody. Anti-Ig stimulates resting B lymphocytes to enlarge, synthesize RNA, increase membrane Ia expression, express activation markers, and become responsive to soluble factors termed B-cell growth factors (BCGF). We have described two different BCGFs, an 18 kd BCGF derived from a T-T hybridoma and a 60 kd BCGF derived from a T cell line. Activated B cells in the presence of BCGF further enlarge; express another activation marker, the transferrin receptor; and enter the S phase of the cell cycle, but do not differentiate unless another factor is present, e.g., B-cell differentiation factor (BCDF). We have described another T-T hybridoma which constitutively secretes both an 18 kd BCGF and a 35 kd BCDF. These two factors can easily be separated by biochemical means. The 35 kd BCDF induces the differentiation of activated but not resting B cells. Besides these B-cell-specific factors, we have studied the immunoregulatory effects of interleukin 1 (IL-1), IL-2, and interferons (alpha and gamma) on human B-cell responses. Interleukin 1 weakly co-stimulates resting B cells when it is present with anti-Ig and enhances the differentiation of activated and proliferating B cells when it is present in culture with BCDF. Interleukin 2 receptors as defined by the monoclonal antibody anti-Tac and radiolabeled IL-2-binding assays are present on in vitro activated B cells. Recombinant IL-2 added to cultures of in vitro activated B cells promotes both B-cell growth and B-cell differentiation into Ig-secreting cells. Finally, interferons appear to have little direct effect on human B-cell function. Major advances in our understanding of the complexities of B-cell activation, proliferation, and differentiation have been realized over the past few years. The eventual isolation and chemical characterization of the soluble mediators of B-cell function and the receptors for these mediators should lead to further insights and to new approaches to those diseases characterized by aberrations of B-cell function.
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PMID:Activation and immunoregulation of human B lymphocytes. 608 41

We have previously shown that the most primitive human hematopoietic cells are included within a cell subpopulation expressing high levels of CD34 and low or undetectable levels of CD45RA and CD71. In this study, cord blood cells with this phenotype were sorted and further separated based on their expression on the Thy-1 antigen. The proliferation and differentiation of the purified cell fractions in response to a mixture of hematopoietic cytokines was analyzed in serum- and stroma-free liquid cultures. Thy-1+ cells (25% of CD34+ CD45RAlo CD71lo cells) were particularly enriched for high proliferative potential colony-forming cells (HPP-CFC; up to 45% of the clonogenic cells), whereas Thy-1- cells were enriched for multipotential colony-forming cells (CFU-MIX; up to 46% of the clonogenic cells). When both subpopulations were cultured in serum-free liquid cultures supplemented with a cytokine mixture that included steel factor, interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-3 fusion protein, M-CSF, G-CSF, and erythropoietin, Thy-1+ cells showed a much higher numerical expansion of CD34+ cells (30,000-fold) and colony-forming cells (4,700-fold) than was observed in cultures initiated with Thy-1- cells (900-fold increase in CD34+ cell numbers and 241-fold increase in CFC numbers). Cells coexpressing CD34 and Thy-1 were only transiently expanded (up to 29-fold) and were not detected after day 22 of culture. When CD34+ CD45RAlo CD71lo Thy-1+ cells were cultured, either in semi-solid or liquid cultures, in the presence of anti-Thy-1 antibody, a significant reduction in progenitor cell numbers (particularly HPP-CFC) was observed. In contrast, CD34+ CD45RAlo CD71lo Thy-1- cells were not affected by anti-Thy-1. The results of this study indicate that Thy-1 is expressed on primitive cord blood progenitors with the highest in vitro proliferative potential, and further suggest that Thy-1 is involved in hematopoietic cell development, possibly by mediating a negative signal that results in inhibition of primitive cell proliferation.
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PMID:Thy-1 expression is linked to functional properties of primitive hematopoietic progenitor cells from human umbilical cord blood. 751 97


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