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)

Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25-dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin-1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma.
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PMID:Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. 786 50

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA-5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.
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PMID:Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. 791 45

In crescentic glomerulonephritis, crescent formation involves the active participation of glomerular epithelial cells (GEC) and macrophages recruited to the glomerulus during the evolution of the disease. Cytokines derived from macrophages may affect many functions of GEC. In this study, we found that interleukin-1 beta (IL-1 beta) inhibited GEC growth (DNA synthesis and cell number) in vitro in a dose- and time-dependent manner. This effect was not mediated by tumor growth factor beta (TGF beta) which is a potent inhibitor of GEC growth in vitro. Treatment of GEC with various concentrations of IL-1 beta induced morphologic changes consisting in the loss of their cobblestone shape and acquisition of a fibroblast-like appearance. Moreover, IL-1 beta was shown to stimulate the expression of interleukin-6 (IL-6) by GEC. The increase in IL-6 secretion by GEC treated with IL-1 beta was observed at both the protein and mRNA levels. IL-1 beta also affected the metabolism of laminin in cultured GEC, inducing a dose-dependent increase in laminin production in culture supernatants harvested from GEC. Finally, we investigated the expression of MHC class II antigens and intercellular adhesion molecule-1 (ICAM-1) in GEC, and found that unstimulated GEC are negative for MHC class II antigens, as detected by flow cytometry. In contrast to the induction of effector functions, expression of MHC class II antigens stringently required interferon-gamma. IL-1 beta did not induce MHC class I antigen expression. The regulation of ICAM-1 expression in that unstimulated GEC expressed ICAM-1, and this expression was upregulated by IL-1 beta. We conclude that IL-1 beta alters many functions of GEC, and these changes may be involved in the initiation and amplification of glomerular injury.
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PMID:Interleukin-1-beta activation of cultured glomerular epithelial cells. 792 73

Interleukin-6 (IL-6) is a multifunctional cytokine which plays a role in the stimulation, inhibition, differentiation, and regulation of cell growth. IL-6 has been shown to act as an autocrine growth factor in several tumors, and is expressed by a variety of tumors. IL-6 also exhibits a regulatory role in the hypothalamo-pituitary axis. It is produced by both the hypothalamus and the pituitary, and it induces the secretion of anterior pituitary hormones. Because of the regulatory role of IL-6 in tumor growth and its involvement in the pituitary, we decided to evaluate IL-6 and IL-6 receptor expression in pituitary tumors. For this purpose we utilized complimentary cDNA probes specific for the IL-6 and IL-6 receptor mRNA, as well as monoclonal anti-IL-6 antibodies for immunohistochemical analysis. Our results show that the IL-6 gene is expressed in the normal pituitary tissue. However, the non-functioning and functioning pituitary tumors such as the prolactin and growth hormone secreting tumors express increased levels of the IL-6 gene. The IL-6 receptor gene was only expressed in the prolactin secreting and non-functioning pituitary tumors. These results show that the IL-6 and IL-6 receptor gene expression is enhanced in pituitary tumors, thus suggesting a possible role of IL-6 in the pathogenesis of these tumors.
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PMID:Interleukin-6 and interleukin-6 receptor gene expression in pituitary tumors. 796 88

Interleukin-6 (IL-6) mediates pleiotropic functions through specific receptors (IL-6R) composed of an 80-kDa binding protein, associated with a non-ligand binding protein (gp130) which transduces the signal. Because IL-6 is the major tumor growth factor in multiple myeloma, we investigated the regulation of IL-6R in two human multiple myeloma cell lines. Binding experiments with 125I-labeled IL-6 showed that IL-6R were expressed at a high density on RPMI-8226 cells (15 000 receptors/cell), but no specific binding was detected on XG-1 cells, whose growth depends on the presence of exogenous IL-6. However, when IL-6 was removed from the culture medium, high-affinity IL-6R appeared on the surface of XG-1 cells (5300 sites/cell). Treatment of RPMI-8226 cells with IL-6 reduced the number of IL-6R without changing their affinity. This reduction was dose dependent and was not affected by acid treatment which dissociates ligand-receptor complexes. Cross-linking experiments showed that the formation of one IL-6/receptor complex of 160 kDa markedly decreased upon IL-6 treatment, while the other complex of 190 kDa became undetectable. These data provide evidence for ligand-induced down-regulation of membrane IL-6R expression in myeloma cells. Treatment of RPMI-8226 cells with interferon-alpha (IFN-alpha), which inhibits the growth of these cells, stimulated IL-6R expression and increased the formation of the 160-kDa IL-6/receptor complex. This stimulation was specific for IFN-alpha, since IFN-gamma reduced the number of IL-6R. These data indicate that, in myeloma cells, IL-6R are differentially regulated by IL-6 and IFN-alpha.
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PMID:Differential regulation of interleukin-6 receptors by interleukin-6 and interferons in multiple myeloma cell lines. 802 May 47

We established a cancer cachexia model in BALB/c mice bearing Colon 26 and examined antitumor and anticachectic activity of UFT. The mice bearing Colon 26 showed a progressive loss of body weight, loss of lipid, and hypalbuminosis associated with the change of tumor size and these symptoms were improved by removal of cancer. In this model UFT extended life span significantly at 15mg/kg/day though showed a little growth inhibitory activity. UFT showed a significant tumor growth inhibitory activity and extended life span at 20mg/kg/day and could reverse all biological parameters mentioned above. Since the intratumor and plasma contents of IL-6 were significantly lowered in the UFT administered group, it is estimated that the anticachectic activity of UFT originates from reduction of interleukin-6 in tumor.
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PMID:[Antitumor and anticachectic activity of UFT in BALB/c mice bearing colon 26 adenocarcinoma]. 808 52

In order to define the potential antitumor activity of the multifunctional cytokine interleukin-6 (IL-6), retrovirus-mediated gene transfer was used to introduce and express a cDNA encoding human IL-6 in the murine fibrosarcoma cell line Fsa-R. Although these genetically modified tumor cells appeared morphologically and phenotypically identical to control Fsa-R cells and had a similar plating efficiency in vitro, they were found to exhibit greatly reduced tumorigenicity in vivo following intravenous injection into syngeneic recipients. Exogenous IL-6 was shown to produce a similar inhibition of tumor growth in the lung if administered intraperitoneally. In contrast, tumor growth in subcutaneous sites was inhibited only if the tumor cells were engineered to express IL-6 locally, or if IL-6 was administered intratumorally. Intraperitoneal injection of IL-6 had no inhibitory effect. Tumors that did grow from IL-6-producing tumor cell inocula in subcutaneous sites were found to contain large numbers of macrophages. These results demonstrate that the antitumor activity of systemically administered IL-6 varies depending on the site of tumor growth and suggest an important role for IL-6 in the recruitment, proliferation and/or survival of tumor-associated macrophages.
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PMID:Inhibitory effect of locally produced and exogenous interleukin-6 on tumor growth in vivo. 816 16

Interleukin-6 is a pleiotropic cytokine and may be a pivotal mediator in the pathogenesis of shock and sepsis, in modulating megakaryocytopoiesis, and in inhibition of tumor growth. Among characteristics of interleukin-6 are regulation of expression of other cytokines, induction of differentiation and proliferation of normal and malignant cells, and inhibition of tumor growth in vivo under experimental conditions. As a major inducer of the acute phase response, interleukin-6 is produced and sets off a chain of events as it acts on effector targets. Preclinical anti-tumor studies with interleukin-6 have provided rationale for probing its role in the therapy of malignancy. The probability is that in the near future interleukin-6 will have established clinical roles as a protein of diagnostic and therapeutic import.
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PMID:Interleukin-6: a cytokine with potential diagnostic and therapeutic roles. 820 Dec 59

Temporal patterns of the cachectic effects of tumor growth and their relation to systemic levels of tumor necrosis factor (TNF) and IL-6 (interleukin-6) were examined in a rat model of experimental cancer cachexia employing the methylcholanthrene (MCA) sarcoma. Fischer 344 rats, implanted with biotelemeters for measuring temperature and activity, were implanted subdermally with tumor tissue fragments. Ad libitum-fed and pair-fed controls were sham incised. Bioassays for TNF and IL-6 were performed on serial plasma samples, obtained via jugular vein at 3- to 6-day intervals throughout the experimental period. Tumor growth induced significant anorexia, weight loss, and a decline in motor activity corresponding to an increase in mean plasma IL-6 levels, independent of reduced food intake or weight loss alone as shown in pair-fed controls. A significant lowering of body temperature then developed, followed by a two- to threefold increase in water consumption. The patterns of weight loss and temperature reduction differed in rate and degree from those seen with pair feeding.
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PMID:Experimental cachexia: effects of MCA sarcoma in the Fischer rat. 836 92

Cachexia is a common problem in the clinical management of cancer patients, particularly those with solid tumors. Cachexia is most obviously manifested as weight loss with massive depletion of both adipose tissue and muscle mass, and death is probably due to loss of lean body tissue. Not only is the survival time shorter in patients with cachexia, but the frequency of response to chemotherapy is also significantly reduced. Although anorexia frequently accompanies cachexia, attempts to halt or reverse cachexia by nutritional repletion have not been successful. This suggests that cachexia is due to metabolic abnormalities produced by the tumor in addition to the underlying anorexia. In some patients weight loss is associated with an increased relative energy expenditure possibly through an elevated adrenergic state. Several factors have been postulated as mediators of cancer cachexia and can be divided into two groups. (i) Materials with hormone-like characteristics which result in direct catabolism of host tissues. (ii) Cytokines which cause alterations in host metabolism indirectly. Included in group (i) are the conventional catabolic hormones and a lipid mobilizing factor (LMF) produced by tumors, which causes direct breakdown of adipose tissue. Included in group (ii) are tumor necrosis factor-alpha, interleukin-6, interferon-gamma and leukaemia inhibitory factor. The materials appear to influence adipose tissue indirectly through an inhibition of lipoprotein lipase. Reversal of cachexia has been achieved by two groups of agents. (i) Those stimulating food intake, e.g. megestrol acetate. (ii) Those directly inhibiting the LMF, e.g. eicosapentaenoic acid. While agents in group (i) can cause tumor growth stimulation, those in group (ii) act as tumor growth inhibitors. This latter results suggests that the products of catabolism of host tissues may be important for tumor growth and provides a new avenue for chemotherapeutic intervention.
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PMID:Cancer cachexia. 849 Jan 91


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