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)

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

Expression patterns of interleukin-6 (IL-6), IL-6 receptor (IL-6R), and gp130 genes in 39 patients with acute myeloid leukemia (AML), in 23 patients with acute lymphoblastic leukemia (ALL), and in 7 patients with acute mixed lineage leukemia (AMLL) were studied by quantitative reverse transcriptase-polymerase chain reaction. Significant levels of IL-6 were expressed in 8 (21%) of 39 AML patients and in 2 (29%) of 7 AMLL patients, whereas in ALL, the expression of IL-6 was almost negligible. IL-6R was expressed in all patients with AML and AMLL, whereas only half of ALL patients expressed low levels of IL-6R as compared with those with AML and AMLL. However, gp130 was ubiquitously expressed in all the leukemia patients, and there was no significant difference in gp130 expression among AML, ALL, and AMLL. Significant correlation was observed between the expression of IL-6R and gp130 in AML. When tested for in vitro response to IL-6, the leukemic cells from 3 of 7 AML, none of 3 ALL, and both of 2 AMLL patients significantly responded to IL-6, showing the correlation between the expression levels of IL-6R and gp130 and the responsiveness of leukemic cells to IL-6. These results showed that quantitation of IL-6R and gp130 expression by reverse transcriptase-polymerase chain reaction is useful for the rapid prediction of the responsiveness of leukemic cells to IL-6, especially in cases of administration of IL-6.
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PMID:Expression of the interleukin-6 (IL-6), IL-6 receptor, and gp130 genes in acute leukemia. 791 80

High-dose methylprednisolone (HDMP, 20-30 mg/kg/day po) treatment has been shown to increase the number of bone marrow and peripheral blood CD34 positive progenitors and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in patients with ALL and AML. To investigate the effect of HDMP on some other hematopoietic regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (gamma-INF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were studied by microplate ELISA technique in 15 chemotherapy-induced neutropenic episodes of 14 children with acute leukemia (eight with ALL and six with AML) in whom HDMP was given alone (30 mg/kg/day po) for 4 days. The absolute neutrophil counts increased significantly in all neutropenic episodes on the fourth day of HDMP treatment. The TNF-alpha was 93.5 +/- 161 pg/ml in ALL and 78.3 +/- 61.4 pg/ml in AML before treatment and 76.1 +/- 160 pg/ml in ALL and 19.1 +/- 39.8 pg/ml in AML after treatment. The gamma-INF was 204.1 +/- 210.3 pg/ml in ALL and 130.8 +/- 138.3 pg/ml in AML before treatment and 28.6 +/- 50.5 pg/ml in ALL and 23.3 +/- 20.4 pg/ml in AML after treatment (P<0.05). Serum G-CSF and GM-CSF levels increased in all episodes (100%). The GM-CSF levels increased from 12.2 +/- 10.9 pg/ml to 36 +/- 24.7 pg/ml after treatment in ALL (P<0.05) and from 13.3 +/- 4 pg/ml to 45 +/- 48.1 pg/ml in AML (P<0.05). Serum G-CSF levels increased from 13.3 +/- 11.7 pg/ml to 83.3 +/- 86.8 pg/ml after treatment in ALL (P<0.05) and from 6.6 +/- 12.1 pg/ml to 28.3 +/- 11.3 pg/ml in AML (P<0.05). However, IL-6 levels were undetectable in all patients before and after therapy. These preliminary data suggest that short-course HDMP treatment could decrease serum TNF-alpha and gamma-INF and increase G-CSF and GM-CSF levels.
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PMID:Serum TNF-alpha, gamma-INF, G-CSF and GM-CSF levels in neutropenic children with acute leukemia treated with short-course, high-dose methylprednisolone. 863 22

We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6-Pseudomonas exotoxin (IL6-PE4E) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE4E in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50% decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 10(3) ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE4E may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease.
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PMID:Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation: a possible target for therapy with recombinant IL6-Pseudomonas exotoxin. 932 1

The tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) mRNA accumulation and the release of the cytokines TNF-alpha and IL-6 was determined in leukemic cells isolated from bone marrow biopsy from patients with acute lymphoblastic leukemia: ALL-common type (cALL), 11 patients; ALL-T type, nine patients. The non-leukemic bone marrow cells (BMMC) and peripheral blood mononuclear cells (PBMC) from healthy donors were used as a control. The mRNA was assessed by fluorescent in situ hybridization in cell suspension and analyzed with flow cytometry. The accumulation of cytokine mRNA was higher in cALL cells as compared to ALL-T and PBMC (control) and was comparable to cytokines mRNA accumulation in BMMC. The production of IL-6 by leukemic cells from both types of leukemia was significantly lower than in BMMC. The bioactive TNF was not detected in either of the leukemia groups studied. TNF-alpha protein was produced by ALL-T cells and BMMC but not by cALL type of leukemic cells. The synthesis of IL-6 was significantly enhanced by TNF-alpha in BMMC and ALL-T while the presence of TNF-alpha had no effect on IL-6 synthesis in the culture of cALL leukemic cells. It was concluded that despite IL-6 and TNF-alpha mRNA contents, leukemic cells representing early stage of B-cell development (CD10+) showed disregulation of production of these cytokines.
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PMID:The IL-6 gene expression by leukemic cells from acute lymphoblastic leukemia common and T type and modulation of IL-6 production by TNF. 972 2

Chemokines play an important role in leukocyte mobilization, hematopoiesis, and angiogenesis. Tissue-specific expression of particular chemokines also influences tumor growth and metastasis. Here, the CC chemokine pulmonary and activation-regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC immunoreactivity was consistently detected in plasma from healthy donors. After purification to homogeneity, the presence of intact PARC (1-69) and processed PARC (1-68) in normal human plasma was confirmed by sequence and mass spectrometry analysis. Furthermore, PARC serum levels were significantly increased in children with T-ALL and prepreB-ALL compared to control serum samples, whereas serum levels in AML and preB-ALL patients were not significantly different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC-1)/CCL14 was not found to be a biomarker in any of these patients' strata, whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients produced IL-8/CXCL8 or macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3) but not PARC, not even after IL-4 or IL-10 treatment. However, PARC was produced by superantigen or IL-4 stimulated monocytes co-cultured with lymphocytes or lymphoblastic cells. Serum PARC levels thus constitute a novel leukemia marker, possibly reflecting tumor/host cell interactions in the circulation.
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PMID:PARC/CCL18 is a plasma CC chemokine with increased levels in childhood acute lymphoblastic leukemia. 1457 5

Immunostimulatory DNA containing unmethylated cytosine-phosphate-guanosine (CpG) induces the development of T helper 1 (Th1) immune responses. The response of B cells to CpG stimulation involves increased proliferation, cytokine production, and costimulatory molecule expression. Similar effects have been observed following CpG stimulation of a variety of malignant B cells. Pediatric precursor B acute lymphoblastic leukemia (B-ALL) cells express low levels of costimulatory molecules and are generally poor stimulators of T-cell responses. In this study, we evaluated the impact of CpG stimulation on precursor B-ALL cell lines and pediatric patient-derived samples. The ability to respond to CpG oligodeoxynucleotides was determined by the level of Toll-like receptor 9 (TLR9) expression. In contrast to both nonleukemic B-cell precursors and mature B cells, the response of precursor B-ALL cells was characterized by increased CD40 expression but only small changes in CD86 levels and no induction of CD80 expression. CpG stimulation of ALL blasts produced increased levels of interleukin-6 (IL-6), IL-8, and IL-10 but no detectable IL-12p70 and led to a skewing of allogeneic T cells, with enhanced interferon gamma (IFN-gamma) production and reduced secretion of IL-5. These results demonstrate the functional relevance of CpG stimulation of precursor B-ALL cells and provide a rational basis for study of these agents for use in treatment of this disease.
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PMID:CpG stimulation of precursor B-lineage acute lymphoblastic leukemia induces a distinct change in costimulatory molecule expression and shifts allogeneic T cells toward a Th1 response. 1565 62

We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.
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PMID:Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice. 1952 Aug 6

The prevalence of depression among patients diagnosed with cancer is higher than general population and is associated with faster tumor progression and shorter survival time. Cytokines whose primary function is to act as signaling molecules of the immune system have recently also been implicated in the pathogenesis of depression. The aim of present study was to investigate the relation between pro-infammatory cytokines [Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha)], depression and stressful life events in patients with acute leukemia. Twenty eight patients (18 males and 10 females) suffering from acute leukemia participated in this study. Their mean age was 33.3 +/- 12.1 years. They were subjected to psychiatric assessment using The Beck Depression Inventory (BDI), Holmes and Rahe Social Readjustment Scale, The Perceived Stress Scale (PSS) and The Brief Fatigue Inventory (BFI). Measurement of IL-6 and TNF-a genes expression in peripheral blood mononuclear cells was done using real-time PCR. Results revealed statistically significant elevation in the level of IL-6 gene expression, fatigue and perceived stress among depressed patients compared to none depressed group. The same results were obtained when comparing patients exposed to moderate or severe stressful life events compared to those exposed to none or mild stressful life events. Although, TNF-a gene expression was not associated with depression or stressful life events, it was associated with acute myeloblastic leukemia (AML). IL-6 gene expression was much higher among patients with AML than acute lymphoblastic leukemia (ALL), but the difference did not reach statistical significance. These findings support the hypothesis that IL-6 might be involved in the etiology and symptomatology of depression in cancer patients. The development of biologic therapies targeting IL-6 may raise the possibility of simultaneously countering the severe effects of depression.
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PMID:Pro-inflammatory cytokines and depression in patients with acute leukemia. 2030 66

Obesity is associated with an increased incidence of many cancers, including leukemia, although it is unknown whether leukemia incidence is increased directly by obesity or rather by associated genetic, lifestyle, health, or socioeconomic factors. We developed animal models of obesity and leukemia to test whether obesity could directly accelerate acute lymphoblastic leukemia (ALL) using BCR/ABL transgenic and AKR/J mice weaned onto a high-fat diet. Mice were observed until development of progressive ALL. Although obese and control BCR/ABL mice had similar median survival, older obese mice had accelerated ALL onset, implying a time-dependent effect of obesity on ALL. Obese AKR mice developed ALL significantly earlier than controls. The effect of obesity was not explained by WBC count, thymus/spleen weight, or ALL phenotype. However, obese AKR mice had higher leptin, insulin, and interleukin-6 levels than controls, and these obesity-related hormones all have potential roles in leukemia pathogenesis. In conclusion, obesity directly accelerates presentation of ALL, likely by increasing the risk of an early event in leukemogenesis. This is the first study to show that obesity can directly accelerate the progression of ALL. Thus, the observed associations between obesity and leukemia incidence are likely to be directly related to biological effects of obesity.
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PMID:Diet-induced obesity accelerates acute lymphoblastic leukemia progression in two murine models. 2082 91


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