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)

CD44 variant isoforms (CD44v) are generated by alternative splicing of the nuclear RNA resulting in the expression of additional protein domains in the extracellular region of the CD44 standard molecule (CD44s). In multiple myeloma (MM), CD44 mediates binding of tumor cells to stroma and regulates interleukin-6 production. To evaluate the role of CD44v isoforms in MM, CD44v expression was analyzed by immunohistochemical staining of 64 bone marrow biopsies from 38 MM patients. Expression of variant isoforms containing the 9v domain was observed in 36% of cases and was associated with an advanced stage (P < .02; n = 61), a progressive disease (P < .001; n = 61), and a shorter overall survival (P < .02; n = 36). In contrast, 3v, 4v, 6v, or 10v isoforms were detected only in a small percentage of the patients. To analyze the exon composition in RNA-transcripts, reverse transcriptase polymerase chain reaction analyses followed by Southern hybridization with exon-specific probes were performed in fluorescence-activated cell sorted myeloma plasma cells. Tumors expressing the 9v domain showed complex, 9v-containing transcripts in combinations with the 3v, 7v, 8v, and 10v exons. Identical transcripts were detected in several myeloma cell lines and in a Ki-1 B-immunoblastic lymphoma. Similar to high-grade non-Hodgkin's lymphoma and gastric and renal cell carcinoma, overexpression of 9v-containing isoforms in MM is related to an unfavorable clinical presentation and represents a new prognostic parameter.
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PMID:Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. 887 9

Interleukin-6 (IL-6) is a cytokine with pleiotropic biologic activities on B cells, T cells, and hematopoietic progenitors. The present study was undertaken to assess pharmacodynamic effects of subcutaneous administration of IL-6 on blood counts, immunologic parameters, and acute-phase reactants. Blood samples were taken from patients with advanced renal cell cancer participating in a phase II trial of recombinant human IL-6. Multiparameter FACS analyses of peripheral blood mononuclear cells were performed using antibodies against CD3, CD4, CD8, HLA-DR, CD56, CD28, CD38, CD19, sIgM, and sIgG. Serum levels of IL-10, soluble CD23 (sCD23), sCD25, IL-1 receptor antagonist protein (IL-1RA), soluble tumor necrosis factor (TNF) receptors (sTNF-R) p55 and p75, and soluble IL-6 receptor (sIL-6R) were detected by ELISA systems. Levels of C-reactive protein (CRP), neopterin, fibrinogen, beta 2-microglobulin, and immunoglobulins M, G, and A were measured by standard methods. In response to administration of IL-6, a significant increment in platelet counts was observed, reaching peak levels after 21 days of treatment. In contrast, leukocyte subsets remained unaffected. No change in number of immunophenotype of peripheral blood B cells, T cells, or natural killer cells could be detected following IL-6 administration. Blood levels of sCD23, IL-10, sIL-6R, neopterin, beta 2-microglobulin, and immunoglobulin subsets were not influenced by cytokine therapy. However, administration of IL-6 led to a slow increment of acute-phase reactants CRP and fibrinogen. Furthermore, the anti-inflammatory molecules sTNF-R p55 and p75 were induced by IL-6, whereas serum levels of IL-1RA remained unchanged. Finally, an increase in blood levels of sCD25 was observed. In conclusion, IL-6 in vivo predominantly acts as a regulator of inflammation and a megakaryocyte differentiation factor.
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PMID:Immunomodulatory and hematopoietic effects of recombinant human interleukin-6 in patients with advanced renal cell cancer. 893 65

Interleukin-6 (IL-6) is a multifunctional cytokine with many biologic activities in vitro, including synergistic or antagonistic actions with one or more other cytokines. The role and induction parameters of IL-6 in renal cell carcinoma (RCC) are not fully understood. To understand the ability of RCC to produce IL-6, we determined the IL-6 concentration in the supernatant of histocultured human normal kidney, RCC, renal Wilms' tumor and renal oncocytoma. From these studies, we conclude that the kidney is one of the main sources of IL-6. Normal renal cortical tissues and renal tumors can produce IL-6 in histoculture without stimulation. Thus histoculture supports the long-term production of IL-6, potentially allowing many important studies of this cytokine in the normal and malignant kidney.
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PMID:Interleukin-6 production in primary histoculture by normal human kidney and renal tumor tissues. 906 39

Two renal cell carcinoma (RCC) cell lines, JMSU2 and JMSU3, derived from the primary sites of mixed cell type and spindle cell type RCC, respectively, have been established and maintained for 31 and 22 months. Karyotypic analysis revealed human karyotypes with modal numbers of 84 and 55, respectively. Consistent chromosomal abnormalities were 1p+, 3p-, 6q- or 8p- in the JMSU2 cells and 1p-, inv (5p + q-) or loss of sex chromosome in the JMSU3 cells. Electron microscopy revealed abundant glycogen granules, lipid droplets and microvilli. The JMSU3 cells transplanted to nude mice produced tumors with a spindle cell pattern similar to that of the original tumor. High concentrations of cytokines, such as interleukin-6 (145,000 pg/ml), interleukin-8 (35,300 pg/ml) and granulocyte-colony stimulating factor (6,340 pg/ml), were detected in the culture supernatant of the JMSU3 cells. Interleukin-1 beta (IL-1 beta) dose-dependently inhibited the proliferation of the JMSU2 and JMSU3 cells in culture. Tumor cytotoxic factor/hepatocyte growth factor (TCF/HGF) dose-dependently enhanced JMSU3 cell proliferation, but suppressed JMSU2 cell proliferation. These findings suggest that IL-1 beta and TCF/HGF have regulatory roles in the proliferation of RCC.
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PMID:[Establishment of two renal cancer cell lines]. 912 51

Measurement of body temperature is the most common clinical test performed. The presence of fever is accepted as a reliable indicator of either acute of chronic disease. Although the vast majority of fevers are caused by infectious agents, some solid tumors have fever as a presenting illness usually because of associated inflammation or infection secondary to the neoplasm. However, cancer cells can spontaneously produce cytokines, small proteins with multiple biological properties. Some cytokines released by neoplastic cells are pyrogenic, ie, they produce fever directly by their action on the hypothalamic thermoregulatory center. Examples of malignant cells producing pyrogenic cytokines are renal carcinoma, lymphomas, and acute myelogenous and chronic myelogenous leukemias. The pyrogenic cytokines released by these cancers are interleukin-6, interleukin-1, tumor necrosis factor, and interferon, but others likely exist. Antipyretics reduce fever regardless of its causation; some studies suggest that fever caused by pyrogenic cytokines released from malignancies is preferentially reduced by nonsteroidal anti-inflammatory agents.
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PMID:Fever. 920 85

Patients with malignancies often present with signs of inflammatory reactions such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Since interleukin-6 (IL-6) is a possible regulator of these reactions and has been proposed as a predictor of prognosis, the aim of the study was to analyse its clinical significance in patients with renal cell carcinoma. Serum samples were collected from 196 patients before any treatment. IL-6 was analysed by an enzyme-linked immunoassay and compared with tumour grade, stage, acute-phase reactants and survival. Patients with renal cell carcinoma had significantly higher IL-6 levels (mean 28.1 +/- 63.4 ng/l; median 8.3 ng/l) compared with controls (mean 1.7 +/- 2.6 ng/l; median 0.5 ng/l; P < 0.001). Serum IL-6 levels in patients with distant metastases were significantly higher than for patients with tumours confined to the kidney (P = 0.02). This difference was more pronounced when serum IL-6 levels in patients with poorly differentiated tumours were compared with well-differentiated tumours (P < 0.001). A significant correlation between the acute-phase reactants CRP, ESR and IL-6 levels was found. Survival time was significantly shorter (P = 0.001) for patients with IL-6 levels above the median serum level compared with patients with lower levels. Similar significant prognostic results were obtained in the group of patients with metastatic disease, but not in group of patients with stage I-III. Serum levels of IL-6 correlated to tumour stage, grade and acute-phase reactants. Increased levels were related to the presence of metastases and adverse survival. Serum IL-6 proved univariate prognostic information but this prognostic significance was lost using a multivariate analysis.
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PMID:Serum interleukin-6 in relation to acute-phase reactants and survival in patients with renal cell carcinoma. 947 Aug 35

The LYT-10 gene was initially cloned by virtue of its disruption by the translocation breakpoint in some t(10;14) lymphoid neoplasms. LYT-10 is now known to encode a component of the NF-kappaB family of transcriptional activators and has therefore also been designated NFkappaB2. Activation of NF-kappaB is generally associated with its transfer to the nucleus and is followed by a rapid increase in expression of its target genes, which include cytokines such as interleukin-6 (IL-6). IL-6 can also be induced by other transcription factors such as NF-IL6. We studied the interaction of IL-1 and these transcription factors in two renal cell carcinoma cell lines (ACHN and Caki-1). These lines produce high levels of IL-6, show endogenous chloramphenicol acetyltransferase activity for the IL-6 promoter, and have high basal levels of transcripts encoding the NF-kappaB components Lyt-10, p50, and p65 as well as the NF-IL6 transcription factor. IL-1alpha and IL-1beta markedly increased steady-state levels of LYT-10 (NFkappaB2) transcripts and nuclear Lyt-10 protein in both cell lines. Levels of the NFkappaB1 (p50-encoding), p65, and NF-IL6 transcripts also increased after IL-1 exposure. These changes were accompanied by a 20-fold or greater increase in levels of IL-6 messenger ribonucleic acid (mRNA) and protein. Our observations suggest that the mechanism by which IL-1alpha or IL-1beta induces IL-6 may be mediated through increases in LYT-10 mRNA and protein levels as well as increases in expression of other transcription factors (NFkappaB1, p65, and NF-IL6), in addition to the known ability of IL-1 to post-translationally activate NF-kappaB.
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PMID:Interleukin-1 increases expression of the LYT-10 (NFkappaB2) proto-oncogene/transcription factor in renal cell carcinoma lines. 952 51

Interleukin-6 (IL-6) is produced by renal cell carcinoma (RCC) cell lines and primary tumors. Using immunohistochemical staining in two RCC patients with hypercalcemia and high serum levels of free and total IL-6, we showed expression of IL-6 in metastatic bone tissue. The role of IL-6 in hypercalcemia and bone resorption would suggest that bisphosphonates or dexamethasone could be useful as adjuvant therapy for IL-6 dependent bone metastases which fail to respond to interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA).
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PMID:Enhanced expression of interleukin-6 in bone and serum of metastatic renal cell carcinoma. 956 97

We examined the preoperative and postoperative, urinary levels of the cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in 14 patients with renal cell carcinoma (RCC), and 9 patients who underwent nephrectomy as donors (controls). Although urinary IL-1 beta was measurable in every subject, both IL-6 and TNF-alpha were undetectable in 12 of the 14 patients. None of the urinary cytokines showed levels significantly different from the controls preoperatively. Urinary levels of IL-1 beta showed no correlation with clinical stage or histological grade. Only urinary IL-1 beta was significantly elevated after nephrectomy, when compared with the controls (P < 0.05). However, urinary IL-1 beta showed no correlation with operative blood loss or postoperative infection. These findings suggest that measurement of urinary cytokines is not useful for diagnosis or monitoring of therapy in RCC patients.
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PMID:[Study on urinary levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in patients with renal cell carcinoma]. 958 73

The relationship between the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma (RCC) determined by immunohistochemical staining using the PC10 clone, and the preoperative serum interleukin-6 (IL-6) value determined by ELISA was examined. The secretion of IL-6 in RCC was also examined immunohistochemically using an anti-IL-6 antibody. The PCNA labeling rate was significantly higher in grade 3 tumors than in grade 1 tumors (p < 0.05), but there were no significant differences between the other grades or TNM stages. No significant correlation was obtained between the serum level of IL-6 or the positive cell rate of IL-6 and the pathological grade of the RCC. A correlation was observed between the PCNA labeling rate and positive cell rate, and between the serum IL-6 value and CRP or ESR. In conclusion, the secretion of IL-6 was detected in RCC tissue, and was suggested to be a tumor factor responsible for the growth and spread of RCC. The serum IL-6 value is considered to reflect the total secretion of IL-6 produced by the RCC and accessory cells, i.e., monocyte-macrophage lineage cells, endothelial cells and fibroblasts.
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PMID:[The relationship between the production of interleukin-6 and the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma]. 961 18


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