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 effects of deoxynivalenol (DON or vomitoxin) and four closely related 8-ketotrichothecenes on proinflammatory cytokine and chemokine production were evaluated in a clonal human macrophage model. U-937 cells, which represent a human monocytelike histocytic lymphoma, were differentiated into macrophages by preincubation with phorbol 12-myristate 13-acetate (PMA). Differentiated macrophages were incubated with DON in the absence or presence of lipopolysaccharide (LPS), and supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA) for the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and for the chemokine interleukin-8 (IL-8). In the absence of LPS, DON at 500 or 1,000 ng/ml upregulated TNF-alpha production as early as 3 h and up to 6 h, whereas 100 to 1,000 ng/ml of DON significantly increased production of IL-6 from 3 to 24 h and IL-8 from 6 to 48 h. In cells costimulated with 0.2 microg/ml LPS, DON at 500 or 1000 ng/ml markedly superinduced TNF-alpha and IL-8 production. Although 100 ng/ml of DON also potentiated LPS-induced IL-6 production, 500 or 1,000 ng/ ml of the toxin suppressed the LPS-induced IL-6 response. Four other 8-ketotrichothecenes, fusarenon X, nivalenol, 3-acetyl DON, and 15-acetyl DON, were also capable of upregulating or suppressing TNF-alpha, IL-6, and IL-8 production at concentrations similar to that of DON. In total, the results suggest that DON and other 8-ketotrichothecenes have the potential to both directly induce and superinduce proinflammatory cytokine and chemokine expression in human macrophages, even at toxin concentrations that are cytotoxic.
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PMID:Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model. 1176 69

We report a 55-year-old Japanese male with CD56+ cutaneous lymphoma. The patient had multiple cervical lymphadenopathy, a red nodule on his neck, and parotid gland nodularity. Histologic features of the biopsied cervical lymph node showed follicular hyperplasia with numerous plasma cells. A biopsied skin specimen of the nodule on his neck demonstrated dense infiltration of atypical large lymphocytes into the dermis. Immunohistochemical study of this specimen revealed CD3+, CD4+, and CD56+ expression in the majority of neoplastic cells. Polymerase chain reaction assays for the detection of Epstein-Barr virus sequences were positive for lymph node and skin DNA. Laboratory examinations showed polyclonal gammopathy, pancytopenia, and high serum interleukin-6 levels. These clinical and histological findings resembled those of multicentric Castleman's disease.
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PMID:CD56-Positive cutaneous lymphoma with multicentric Castleman's disease-like systemic manifestations. 1180 73

The interleukins function as intercellular hormones, possessing the ability to alter the activity of a target cell population. Interleukin-4, secreted by activated T-cells, has shown antitumor activity in vitro against multiple myelomas, lymphoma, chronic myelomonocytic leukemia, and some solid tumors. Early promising clinical studies have shown the efficacy of IL-4 in decreasing the malignant lymphocyte count and in normalizing hematologic parameters in patients with CLL and in inducing transient clinical responses in patients with non-Hodgkin's lymphoma. Interleukin-6 possesses immunomodulating properties including enhancement of NK cell activity and induction of cytotoxic T-cell activity. IL-6 has shown antitumor activity in mice injected with weakly immunogenic syngeneic tumors and has been shown to inhibit in vitro human breast carcinoma and leukemia/lymphoma proliferation through a direct tumor inhibitory effect. Clinical studies investigating the antitumor activity of IL-6 are currently in phase II clinical trials. IL-6 and IL-11 have demonstrated thrombopoietic enhancing activity in primate models and early clinical trials. These agents have a potential application in ameliorating the thrombocytopenia associated with myeloablative chemotherapy. Yet to enter clinical trials, IL-12 has been shown to enhance the lytic activity of nonspecific NK/LAK cells and appears to be more efficient than IL-2 or IFN's in enhancing NK cytotoxicity. IL-12 has also been shown to enhance specific allogeneic human CTL responses and to induce the secretion of IFN-gamma from both resting and activated T and NK cells. In summary, these interleukins are now promising agents under investigation as effective treatment strategies in the oncologic setting.
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PMID:A Review of the New Cytokines: IL-4, IL-6, IL-11, and IL-12. 1183 74

Lymph nodes from 44 patients with Castleman disease (CD) without risk factors for HIV infection were analyzed with polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemical analysis for human herpesvirus 8 (HHV-8) and viral interleukin-6 (vIL-6). PCR detected HHV-8 genome in 2 of 4 cases; ISH detected it in 9 of 16 cases. HHV-8 vIL-6 peptides were detected in 2 of 44 cases. vIL-6- and ISH-positive cells were found in large transformed and small lymphocytes of the follicular mantle, respectively. Of 9 cases of plasma cell (PC) CD that demonstrated HHV-8 genome by PCR or ISH, 1 expressed vIL-6. Clonal populations of PCs in CD by immunohistochemical analysis or immunoelectrophoresis of serum and urine were associated with neuropathy. HHV-8 vIL-6 detection was associated with poor survival and lack of HHV-8 IL-6, with low risk for subsequent lymphoma. Although HHV-8 genome was detected in a considerable number of patients with PC CD, vIL-6 expression was infrequent. Expression of HHV-8 vIL-6 in CD may indicate poor prognosis in patients at risk for lymphoma who may prospectively require more aggressive treatment. The lack of vIL-6 expression in CD with HHV-8 genome suggests that human IL-6 rather than vIL-6 may be the principal pathogenic cytokine.
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PMID:Analysis of the human herpesvirus 8 (HHV-8) genome and HHV-8 vIL-6 expression in archival cases of castleman disease at low risk for HIV infection. 1186 23

We describe a 11-year-old boy with acute myeloid leukaemia who presented with widespread bone disease. Spine X-rays revealed multiple crush fractures and there were multiple hot spots on the bone scan. The bone-mineral density was markedly reduced but there was no hypercalcaemia or hypercalcuria. Bone marrow aspirate revealed 98% blast cells and a balanced translocation between chromosomes 10 and 17 in seven of nine metaphases. Plasma interleukin-6 level before chemotherapy was high at 53 pg/ml. We postulate that the mechanism for bony destruction in this case was similar to that in the adult disease myeloma.
Leuk Lymphoma
PMID:Widespread bone disease in acute myeloid leukaemia. 1191 13

C-reactive protein (CRP) is a nonspecific but sensitive marker of inflammation. Interleukin-6 (IL-6), IL-1, and tumor necrosis factor alpha induce the synthesis of CRP in hepatocytes. Increased CRP level is considered to be an important risk factor for atherosclerosis, myocardial infarction, peripheral vascular disease, and ischemic stroke. It is positively correlated with weight loss, anorexia-cachexia syndrome, extent of disease, and recurrence in advanced cancer. Its role as a predictor of survival has been shown in multiple myeloma, melanoma, lymphoma, ovarian, renal, pancreatic, and gastrointestinal tumors. Measurement of CRP is simple, cheap, and routine and provides valuable information in palliative care.
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PMID:The role of C-reactive protein as a prognostic indicator in advanced cancer. 1193 16

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a cellular dihydrofolate reductase (DHFR) homologue. Methotrexate (MTX), a potent anti-inflammatory agent, inhibits cellular DHFR activity. We investigated the effect of noncytotoxic doses of MTX on latency and lytic KSHV replication in two KSHV-infected primary effusion lymphoma cell lines (BC-3 and BC-1) and in MTX-resistant BC-3 cells (MTX-R-BC-3 cells). Treatment with MTX completely prevented tetradecanoyl phorbol acetate-induced viral DNA replication and strongly decreased viral lytic transcript levels, even in MTX-resistant cells. However, the same treatment had no effect on transcription of cellular genes and KSHV latent genes. One of the lytic transcripts inhibited by MTX, ORF50/Rta (open reading frame), is an immediate-early gene encoding a replication-transcription activator required for expression of other viral lytic genes. Therefore, transcription of genes downstream of ORF50/Rta was inhibited, including those encoding the viral G-protein-coupled receptor (GPCR), viral interleukin-6, and K12/kaposin, which have been shown to be transforming in vitro and oncogenic in mice. Resistance to MTX has been documented in cultured cells and also in patients treated with this drug. However, MTX showed an inhibitory activity even in MTX-R-BC-3 cells. Two currently available antiherpesvirus drugs, cidofovir and foscarnet, had no effect on the transcription of these viral oncogenes and ORF50/Rta. MTX is the first example of a compound shown to downregulate the expression of ORF50/Rta and therefore prevent viral transforming gene transcription. Given that the expression of these genes may be important for tumor development, MTX could play a role in the future management of KSHV-associated malignancies.
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PMID:Transcriptional downregulation of ORF50/Rta by methotrexate inhibits the switch of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 from latency to lytic replication. 1196 35

The effects of linearly polarized light (LPL) and diffuse light (DL) on the in vitro interleukin-6 (IL-6) production in a human B lymphoma cell line (BMNH) and peripheral monocytes of healthy volunteers were compared. Our data show that there was a significant increase of IL-6 and IgM production in BMNH after exposure to LPL. The increase in IgM secretion was a consequence of its autocrine regulation by IL-6, since in the presence of anti-IL-6 and anti-IL-6 receptor antibodies the LPL-induced IgM secretion was abolished. In contrast to the stimulatory effect on B cells, exposure of human mononuclear phagocytes to LPL markedly reduced the production of IL-6 induced by subsequent stimulation of cells with bacterial endotoxin (LPS). The inhibition as most pronounced when suboptimal doses of LPS were applied. Under identical experimental conditions, DL had no effect on the IL-6 and IgM production of either B cells or monocytes.
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PMID:Opposite effect of linearly polarized light on biosynthesis of interleukin-6 in a human B lymphoid cell line and peripheral human monocytes. 1199 54

We report four cases presenting with severe osteoporosis which on further investigation were found to have an underlying lymphoplasmacytoid lymphoma (LPL). Common secondary causes of osteoporosis were excluded in each case. Three of the cases responded to treatment with a biphosphonate. As these lymphomas share some common pathological and clinical features with multiple myeloma (MM) an association with osteoporosis is likely to represent more than a coincidental finding. The incidence of osteoporosis occurring with LPL will become clearer if routine imaging is carried out in patients at presentation. Issues relating to the treatment of the osteoporosis as well as the lymphoma arise in patients that present in this way. Based on the model of bone disease in MM, correlating serum levels of osteoclast activating cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor (TNF) with the actual finding of bone disease provides a basis for future research into the pathogenesis and management of bone disease in these rare forms of low grade non-Hodgkin's lymphoma.
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PMID:Lymphoplasmacytoid lymphoma presenting as severe osteoporosis. 1199 87

Serum soluble interleukin-6 receptors (sIL-6R) have been demonstrated to play an important role in hematopoiesis. We report here that serum sIL-6R levels reflect proliferative kinetics of the progenitors after stimulation by chemotherapy plus granulocyte colony-stimulating factor. Serum sIL-6R were serially evaluated in 26 courses of peripheral blood (PB) stem cell collections in 16 patients using enzyme-linked immunosorbent assay. Expressions of IL-6R and CD34 on PB mononuclear cells were examined by flow cytometric analysis and expressions of IL-6R mRNA were examined by reverse transcriptase polymerase chain reaction. There were no significant differences between the serum sIL-6R levels on day 0 in patients (27.8+/-2.1 ng/ml, mean +/- SEM) and those in controls (27.5+/-1.5 ng/ml). Following chemotherapy the serum sIL-6R levels were significantly decreased, reaching a minimal level on day 14 (22.3+/-1.2 ng/ml, p < 0.01) and then significantly increased to above the baseline levels on day 21 (32.0+/-2.1 ng/ml, p < 0.01). Similar oscillations in the number of white blood cells, IL6R+ cells, CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) in PB could be observed and the peak expression of mRNA was compatible with the expression of antigen. Serum sIL-6R levels on day 17 and 19 were positively correlated with the number of CD34+ cells, IL-6R+ cells, CFU-GM in PB and the number of collected CD34+ cells in leukapheresis products. In addition, when comparing the 2 groups divided by the number of prior chemotherapies, the status of disease or dose of the mobilizing regimen, the serum sIL-6R levels were significantly increased after day 17 in the group that received fewer courses of prior chemotherapy, the group in complete remission and the group of high-dose chemotherapy. These findings indicated that sIL-6R levels do not reflect the hematopoietic ability in the steady state, or the capability of the hematopoiesis after stimulation. Thus, sIL-6R levels may be a marker for the timing of PBSC collection or the prediction of the number of collected CD34+ cells.
Leuk Lymphoma 2002 Mar
PMID:Serum soluble IL-6 receptor levels during the mobilization of stem cells to peripheral blood. 1200 69


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