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) 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.
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PMID:Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma. 154 13

Hyperacute graft-versus-host disease (GVHD), which progresses severely and rapidly, was observed in three patients with acute leukemia transplanted with bone marrow cells from human leukocyte antigens (HLA)-identical and mixed leukocyte reactions (MLR)-negative siblings. Hyperacute GVHD developed in these patients within 7 days after bone marrow transplantation (BMT) and was rapidly aggravated inspite of cyclosporin A (CyA) and short-term methotrexate (MTX) prophylaxis and treatment with bolus methylprednisolone (mPSL). These patients showed markedly increased serum interleukin-6 (IL-6) levels after BMT, whereas other cytokines such as interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and IL-2 were not increased compared with pretreatment levels. These findings suggest that markedly increased IL-6 levels may be related to hyperacute GVHD.
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PMID:Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels. 791 41

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

Thrombocytopenia is a major cause of morbidity following intensive chemotherapy for acute leukemia. Over recent years, there has been an increasing use of platelet transfusions which, although generally efficacious to prevent severe hemorrhage, have associated risks of transmitting blood-borne disease and of alloimmunization. Therefore, there is a clinical requirement for a drug that will reliably alleviate the thrombocytopenia associated with leukemia therapy. The c-mpl ligand thrombopoietin is the most interesting factor for the treatment of thrombocytopenia because of its lineage specificity. Phase I and II studies confirm its biological efficacy to induce rise in platelet count in patients with solid tumors and acute leukemia. Several other pleiotropic hematopoietic growth factors are also currently in clinical trials. These include interleukin-6, interleukin-3, interleukin-11, PIXY321 and stem cell factor. The effects of these cytokines appear to be modest at most and, with the exception of interleukin-11, their side effects are likely to limit their clinical application. Combinations of factors may prove more efficacious approaches to enhance platelet recovery.
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PMID:Thrombopoietic factors potentially useful in the treatment of acute leukemia. 992 79

Multiple myeloma is an incurable plasma cell malignancy in which Ras may be constitutively active either via interleukin-6 (IL-6) receptor signaling or by mutation. Inactivation of Ras may be achieved with farnesyl transferase (FTase) inhibitors a class of drugs which have shown promise in clinical trials particularly in patients with acute leukemia. This report investigates the efficacy of two distinct classes of FTase inhibitors in diverse myeloma cell lines and primary isolates. While Ras signaling has traditionally been linked to myeloma cell growth, we found that these compounds also potently triggered cell death. Death induced by perillic acid (PA) was caspase dependent without evidence of death receptor activation. Apoptosis was associated with mitochondrial membrane depolarization and activation of caspase-9 and 3 but proceeded despite over-expression of Bcl-XL a known correlate of relapsed and chemorefractory myeloma. In addition, Fas ligand and TRAIL mediated apoptosis was potentiated in death receptor resistant (U266) and sensitive (RPMI 8226/S) cell lines. Of clinical relevance, the FTase inhibitor R115777 induced cell death in myeloma lines at doses observed in clinical trials. Furthermore, both R115777 and PA induced cell death in primary isolates with relative specificity. Taken together these preclinical data provide evidence that FTase inhibitors may be an effective therapeutic modality for the treatment of multiple myeloma.
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PMID:Farnesyl transferase inhibitors enhance death receptor signals and induce apoptosis in multiple myeloma cells. 1495 58

The aim of this study was to investigate the growth, immunophenotype and interleukin-6 (IL-6) level of bone marrow stromal cells (BMSC) in patients with acute leukemia (AL) and multiple myeloma (MM). BMSC was cultured by wall-adhesion method and the growth of BMSC was observed. The immunophenotype and cell cycle of BMSC were detected by flow cytometry. The level of interleukin 6 (IL-6) in BMSC culture system was detected by ELISA. The results showed that the primary (17.3 +/- 7.8 days) and continuous (10.3 +/- 3.5 days) growth cycle of BMSC in patients with AL were significantly shorter than those in patients with MM (26.5 +/- 6.3 and 16.5 +/- 4.1 days respectively), and shorter than those in normal controls (25.8 +/- 6.3 and 17.5 +/- 2.4 days) respectively. Similarly, S + G2% (17.4 +/- 3.6%) of BMSC in patients with AL was significantly higher than those in patients with MM (8.5 +/- 2.2%) and in normal controls (8.9 +/- 2.3%). All of the three groups showed positive antigen expressions with CD29 and CD44 were 100%, while CD138, CD34, CD54, CD56 positive were not expressed and CD106 was partially expressed positive. The supernatant IL-6 level of BMSC system in MM patients (1288.5 +/- 736.7 pg/ml) was significantly higher than those in AL patients (859.3 +/- 203.1 pg/ml) and normal controls (850.9 +/- 129.5 pg/ml). It is concluded that the growth, S + G2% of cell cycle and IL-6 level of BMSC in patients with MM, AL and normal control are significantly different, whereas the antigen expressions are similar.
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PMID:[Growth, immunophenotype and interleukin-6 level of bone marrow stromal cells in patients with multiple myeloma and acute leukemia]. 1692 3

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

A 14-year-old boy was admitted in the former hospital with remittent fever, erythematous rash, joint pain, and muscle pain. Antibiotics were ineffectively administered and then, methylprednisolone (mPSL) pulse therapy with methotrexate was introduced under the diagnosis of suspected systemic juvenile idiopathic arthritis (JIA). However, he still had clinical symptoms and signs, and was transferred to our hospital. Re-examination revealed no malignancies including acute leukemia by bone marrow aspiration, no infectious agents by septic work, and no significant increases of antibodies against several viruses including CMV, EBV, HSV, Parvovirus B19, adenovirus, and so forth. FDG-PET demonstrated the accumulation of (18)F-FDG in bone marrows suggesting systemic JIA. Laboratory findings were leukocytosis and granulocytosis, elevated levels of C-reactive protein, D-dimer, ferritin, and interleukin-6. He was finally diagnosed as having severe systemic JIA. Thus, soon after the additional mPSL pulse therapy, tocilizumab (TCZ) was successfully introduced. In conclusion, for systemic JIA patients with severe systemic inflammation, it will be reasonable to introduce tocilizumab earlier than the guideline suggested to reduce side effects of long-term and large amounts of steroids and to protect the transition to macrophage activation syndrome. Further studies will be needed to recommend appropriate timing of tocilizumab introduction.
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PMID:[A case of severe systemic juvenile idiopathic arthritis introduced tocilizumab in early phase of the disease]. 2497 31