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)

The leukemic T-cells of the six patients with T-cell chronic lymphocytic leukemia (T-CLL), four with CD4 and CD45R-positive (CD4+ CD45R*) T-CLL and two with CD8 and CD45R-positive (CD8+ CD45R+) T-CLL phenotype were studied for detailed immunologic phenotypic and functional characteristics. The levels of soluble interleukin-2 receptors were elevated significantly in the serum of all four patients with CD4+ CD45R+ T-CLL. Moreover, the CD4+ CD45R+ T-CLL patients' T-cells, after in vitro stimulation with phytohemagglutinin and concanavalin A, expressed elevated percentages of interleukin-2 receptors on cells and secreted high interleukin-2 activity. The B-cell growth factor (BCGF) activity from three patients with CD4+ CD45R+ T-CLL was enhanced, but B-cell differentiation factor (BCDF) activity of the all T-CLL patients was decreased. Reduced BCGF and BCDF activity of the leukemic T-cells was one possible mechanism of hypogammaglobulinemia detected in two patients with T-CLL. All T-CLL patients' leukemic T-cells had diminished immunoregulatory functional activity in allogeneic mixed lymphocyte reactions. These observations suggest that leukemic T-cells from T-CLL patients have many immunologic functional defects that may be important in their proliferative potential.
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PMID:T-cell chronic lymphocytic leukemia. T-cell function and lymphokine secretion. 173 13

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

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.
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PMID:Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia. 278 98

To explore the pathogenesis of marrow failure in B-cell type chronic lymphocytic leukemia (B-CLL), we have examined the production of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage CSF (GM-CSF) by the adherent cell population of bone marrow (BM) derived from B-CLL patients and their capacity to support hematopoietic cell proliferation. Lipopolysaccharide-stimulated B-CLL stromal cells produced G-CSF and GM-CSF in amounts similar to normal stromal layers, whereas IL-6 production was significantly decreased. Using the blast-colony forming cell assay (BI-CFC) and the classical colony-forming unit granulocyte macrophage (CFU-GM) assay, we found that: (1) marrow stromal cells of B-CLL were able to support only 25% of the BI-CFC growth supported by normal marrow stromal cells; (2) this anomaly was partially corrected by the addition of exogenous IL-6; (3) the colony-stimulating activity (CSA) of the conditioned medium (CM) of B-CLL stromal cells was lower than that of normal CM; (4) that this was the result of the presence of an inhibitor rather that of a growth factor defect; (5) this inhibition could be abrogated by addition of anti-transforming growth factor-beta (TGF-beta) neutralizing antibody; (6) this antibody corrected the deficient colony supportive activity of the B-CLL stromal cells; (7) TGF-beta production by marrow stromal cells was significantly increased in CLL compared with normal; and (8) that this was not caused by the effect of the B-CLL lymphocytes on the stromal cells. It is concluded that this increased TGF-beta production in B-CLL is probably responsible for the decreased IL-6 production by stromal cells and for the inhibiting activity on hematopoietic precursors as well. We hypothesize that TGF-beta generated at a high level by B-CLL marrow stromal cells could play a major role in the pathophysiology of the BM failure seen in advanced stages of B-CLL.
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PMID:Excessive production of transforming growth factor-beta by bone marrow stromal cells in B-cell chronic lymphocytic leukemia inhibits growth of hematopoietic precursors and interleukin-6 production. 769 Dec 58

Monocyte derived cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were determined in cell free plasma after stimulation of heparinized whole blood from chronic lymphocytic leukemia (CLL) patients with lipopolysaccharide (LPS) at 1 microgram/ml for 6 hr. Compared to control donors (390 U/ml), CLL patients in average had eight-fold lower levels of TNF bioactivity (50 U/ml). The depressed levels were observed over a wide range of LPS concentrations (0.01 to 10 micrograms/ml). Furthermore, after stimulation with S. aureus bacteria, CLL samples gave three-fold lower levels, as well. TNF levels were not decreased because of defective bioactivity of TNF, since strongly reduced levels of TNF protein were also detected in an immunoassay. Finally, interleukin-6 levels after LPS stimulation were decreased threefold. Flow cytometry analysis with CD14 antibodies demonstrated comparable numbers of monocytes for control donors and CLL patients (698 +/- 802 and 427 +/- 267, respectively). This suggests that deficient cytokine production was not due to a reduction in monocyte number, but rather to a functional impairment. The deficiency in cytokine production observed after ex vivo stimulation of whole blood from CLL patients suggests that in vivo during bacterial infection, CLL patients will exhibit an inappropriate response as well.
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PMID:Decreased production of TNF and IL-6 in whole blood of CLL patients. 774 Nov 43

Normal human plasma and plasma from patients with chronic lymphocytic leukemia (CLL) were used as growth supplements for the cloning of murine hybridomas. Basal medium, consisting of DMEM with 5% foetal calf serum (FCS) was conditioned with supernatant from a known human IL-6-secreting cell line, BRI-6 (BRI-6-CM), normal human plasma (NHP-DMEM), and plasma from patients with CLL (CLL-DMEM). When compared to conventional feeder layers of macrophages, thymocytes, splenocytes and to feeder CLL cells and BRI-6-CM the numbers of clones formed by growing hybridomas in CLL-DMEM was greatly enhanced with a corresponding increase in the number of antibody-producing clones, as determined by ELISA. NHP-DMEM also enhanced the cloning efficiency. All CM and plasma supplemented medium were examined for the presence of interleukin-6 (IL-6). Of eight CLL plasma samples examined only two had elevated IL-6 levels.
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PMID:Enhanced cloning efficiencies of murine hybridomas using human plasma supplemented medium. 819 93

Tumor necrosis factor (TNF-alpha) acts as a growth stimulatory factor on leukemic B lymphocytes from many patients with chronic lymphocytic leukemia (CLL). Because TNF induces production of interleukin-6 (IL-6), which has been shown to be a growth factor for myeloma and other transformed B cells, we examined the possibility that IL-6 mediates the growth-stimulatory effect of TNF on B-CLL cells. In fact, we found that IL-6 is an inhibitor of B-CLL growth. The addition of recombinant human IL-6 markedly decreased the TNF-induced B-CLL growth, and this decrease was even greater when soluble IL-6 receptor, known to act as IL-6 agonist, was added with recombinant IL-6. Conversely, neutralizing monoclonal antibodies to IL-6 and to the IL-6 receptor potentiated the growth stimulation of TNF on B-CLL cells, in line with the possibility that IL-6 functions as a negative feedback regulator of an autocrine TNF action on these B-leukemic cells. Evidence is presented that production of IL-6 by monocytes and B cells of CLL patients is low, suggesting that administration of IL-6 may be beneficial in CLL to reduce the eventual growth stimulation by TNF and, possibly, also the deficiency in platelets and Ig production in this disease.
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PMID:Interleukin-6 inhibits the proliferation of B-chronic lymphocytic leukemia cells that is induced by tumor necrosis factor-alpha or -beta. 838 26

The present study was designed to define the mechanisms of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) gene regulation in chronic lymphocytic leukaemia of B cell origin (B-CLL). By nuclear run-on analysis, all B-CLL cases displayed high levels of nuclear transcription of the IL-6 and TNF-alpha genes, whereas IL-1 beta gene transcription was only barely detectable. Upon in vitro culture for 1 h, B-CLL cells from different patients were substantially heterogeneous in terms of expression of steady state mRNA levels of IL-1 beta, IL-6 and TNF-alpha even though the pattern of nuclear transcription of these cytokines was only marginally affected by in vitro culture. mRNA stability was then examined and cytokine gene transcripts showed a half life of more than 2 h in cultured B-CLL cells and treatment with cycloheximide (CHX) did not affect cytokine transcript levels in B-CLL cells. These results indicate that: steady state levels of each mRNA do not reflect the rate of nuclear transcription of these cytokines in fresh or cultured B-CLL cells, that purification and in vitro culture of leukaemic cells may amplify cytokine gene expression in B-CLL, and that cytokine gene transcripts are relatively stable in B-CLL.
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PMID:Transcriptional and post-transcriptional regulation of IL-1 beta, IL-6 and TNF-alpha genes in chronic lymphocytic leukaemia. 845 68

There is now good evidence that tumour necrosis factor [TNF] stimulates DNA synthesis of B-chronic lymphocytic leukaemia (B-CLL) cells. The malignant clone produces TNF, and addition of exogenous TNF up-regulates the TNF mRNA in B-CLL cells. Interleukin-6 (rIL-6) may also be important in this growth loop. We studied the interaction of TNF and IL-6 in the regulation of DNA synthesis (3H-TdR uptake), cytokine release and cell survival in CLL cells in vitro. Addition of TNF (100 U/ml over 5 days) enhanced DNA synthesis from 718 +/- 284 (mean cpm +/- SE) to 2730 +/- 545 compared to cells cultured in medium alone (n = 16, p < 0.01). TNF-alpha induced DNA synthesis was inhibited in all cases studied by the addition of anti-TNF monoclonal antibody (5 micrograms/ml) to cell cultures. Spontaneous IL-6 protein release was enhanced in the presence of TNF (100 U/ml and 250 U/ml) by CLL cells at 48 hours of culture 143.6% and 172% (p < 0.05, n = 6). At 120 hours of culture, the increase was 323% and 412.5% (4 of 7 cases) of the control respectively. IL-6 (100 U/ml or greater) increased spontaneous DNA synthesis (3H-TdR uptake) but, in the presence of high concentrations of TNF-alpha, inhibited TNF induced DNA synthesis in a dose dependent manner. Cell survival was reduced in the presence of anti-IL-6 mAb, while IL-6 was able to protect CLL cells from spontaneous apoptosis. These results suggest that IL-6 in an autocrine manner may inhibit DNA synthesis but prolongs survival in CLL cells. Increased serum IL-6 levels were detected in 27 of 50 cases of CLL, the mean level being significantly higher in Rai Stage III and IV cases compared to Rai Stage O-II cases.
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PMID:Interleukin-6 inhibits apoptosis and tumour necrosis factor induced proliferation of B-chronic lymphocytic leukaemia. 872 32

Three hybrids derived from CD5+ B cell chronic lymphocytic leukemia (B-CLL) and their parental B cells were studied for phenotypic evolution, immunoglobulin (Ig), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion. When phenotypic evolution was examined, hybrids showed the loss of classical B cell markers, indicating that they follow the same pattern of phenotypic differentiation as normal B cells. Hybrids displayed spontaneous high Ig secretion, which did not appear to be modified through stimulation by phorbol 12-myristate 13-acetate (PMA), recombinant interferon-gamma (rIFN-gamma) and Staphylococcus aureus Cowan I (SAC). Parental cells secreted minimal amounts of Ig spontaneously or through IFN-gamma and SAC stimulation, whereas PMA succeeded in increasing this secretion. An opposite pattern was observed when TNF-alpha and IL-6 secretion an expression at the mRNA level were assessed in hybrids and parental cells. TNF-alpha and IL-6 were spontaneously secreted by parental cells and this secretion was increased after PMA and SAC stimulation, both cytokine secretion and expression at the mRNA level were negative in hybrid cells. The absence of expression of these cytokines could be explained either by chromosomal loss or by down regulation. These results indicate that when parental CLL cells are induced to differentiate in the heterohybrid model, they acquire high spontaneous secretion of Ig, lose the classical B cell phenotypic markers and down regulate the expression of the cytokines studied.
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PMID:Expression and production of cytokines by heterohybrids and their parental B cells in CLL. 872 9


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