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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

Interleukin-6, a pleiotropic cytokine, appears to play a key role as a physiologically functioning molecule in host defense mechanisms. Previous reports have suggested that dysregulated interleukin-6 production may be involved in lymph node hyperplasia, plasmacytosis, immunoglobulin hyperproduction, thrombocytosis, mesangial cell proliferation and acute phase response, all of which are frequently observed in autoimmune disorders. In this report, we discuss the possible involvement of interleukin-6 in the pathogenesis of a variety of autoimmune diseases and the regulatory mechanism of expression of the interleukin-6 gene.
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PMID:Interleukin-6 in autoimmune disorders. 162 87

We report two patients who developed benign plasmacytosis with multiple skin lesions. The cases were characterized by hyperplasia of mature plasma cells, and polyclonal hypergammaglobulinaemia. One patient had hyperplasia of mature plasma cells not only in the skin, but also extensively in lymph nodes and the retroperitoneal areas around the ureters. The other had plasma cell hyperplasia limited to the skin. Extensive investigations failed to reveal any clinical or laboratory evidence suggesting the presence of any underlying disease accompanying the hypergammaglobulinaemia and/or plasma cell proliferation, such as chronic infectious disease, collagen disease or other chronic inflammatory disorder. Clinically and histologically, the first patient showed features compatible with a diagnosis of systemic plasmacytosis and the second with a diagnosis of cutaneous plasmacytosis. Significant serum interleukin-6 (IL-6) levels were detected in both patients, suggesting that IL-6 may be involved in the pathogenesis of these conditions.
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PMID:Systemic and cutaneous plasmacytosis with multiple skin lesions and polyclonal hypergammaglobulinaemia: significant serum interleukin-6 levels. 163 95

The constitutive production of interleukin-6 (IL-6), a potent hepatocyte-stimulating factor and B cell-differentiating factor, was demonstrated in 3 patients with cardiac myxomas. Tumor cells from the only patient who presented with immunologic features produced 14-23-fold higher levels of IL-6 than those from the 2 patients who lacked such features. A significant serum IL-6 level (56 pg/ml), greater than that observed in patients with active rheumatoid arthritis, was also observed only in this patient, with a subsequent return to an undetectable level after surgical removal of the tumor. This was associated with a regression of the immunologic features. This same patient was observed to have an IL-6-dependent, proliferative polyclonal plasmacytosis of the bone marrow. These observations demonstrate that an overproduction of IL-6 by cardiac myxoma cells, in association with a systemic passage of this IL-6, may be responsible for the immunologic features similar to those observed in true autoimmune diseases such as rheumatoid arthritis.
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PMID:Constitutive production of interleukin-6 and immunologic features in cardiac myxomas. 169 May 43

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reactions, and hematopoiesis. Its receptor system consists of two molecules: a ligand-binding 80-kDa molecule and a non-ligand-binding signal transducer, gp 130, both of which were found to belong to the cytokine receptor family. Deregulated IL-6 gene expression has been implicated as being involved in the pathogenesis of a number of diseases, especially autoimmune diseases and plasma cell neoplasias. In fact, IL-6 transgenic C57BL/6 mice showed a massive polyclonal plasmacytosis with production of autoantibodies and mesangial proliferative glomerulonephritis, indicating that IL-6 plays a critical role in the development of plasma cell abnormalities and glomerulonephritis.
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PMID:Interleukin-6 and its relation to inflammation and disease. 172 89

Interleukin-6 (IL-6) is a pleiotropic cytokine that has been postulated as playing a role in the pathogenesis of multiple myeloma, chronic autoimmune diseases, and alcoholic liver cirrhosis. We generated transgenic mice carrying a fusion between the mouse metallothionein-I (MT-I) gene promoter and the human IL-6 cDNA. MT-I/IL-6 transgenics express IL-6 constitutively in the liver and secrete the cytokine in the blood. They show initially activation of acute-phase response genes and accumulation of alpha 2- and beta-globulins in the plasma, which is followed by polyclonal hypergammaglobulinemia. MT-I/IL-6 transgenics die between 12 to 20 weeks of age. Histologic examination of transgenic animals at different ages and after necropsy showed, as expected from previous studies of IL-6 disregulation in vivo, an increase in the number of megakaryocytes in the spleen and bone marrow and, at later stages, IgG plasmacytosis in the spleen, lymph nodes, and thymus. However, no plasma cell infiltration was detected in other organs. The distinguishing feature of MT-I/IL-6 transgenics is the development of a progressive kidney pathology, in which the initial membranous glomerulonephritis is followed by focal glomerulosclerosis and finally by extensive tubular damage that reproduces the damage observed in patients at terminal stages of multiple myeloma (myeloma kidney). The pathogenetic role of IL-6 overproduction and of the resulting serum protein overload in the kidney damage is discussed.
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PMID:Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. 751 4

We describe a case of primary multiple cutaneous plasmacytosis successfully treated by intralesional steroid therapy. Plasma interleukin-6 (IL-6) levels reduced in parallel with the disease activity. Intralesional steroid reduced IL-6 production by peripheral blood mononuclear cells, while neither PUVA therapy nor intralesional recombinant interferon-gamma resulted in a benefit and plasma IL-6 levels did not decrease. It was suggested that IL-6 might play an important role in the pathogenesis of this condition.
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PMID:Intralesional steroid-therapy-induced reduction of plasma interleukin-6 and improvement of cutaneous plasmacytosis. 759 90

We report a patient with anti-glomerular basement membrane disease who developed renal failure associated with systemic manifestations, including acute-phase inflammatory reactions and plasmacytosis. Renal tissue obtained by an open surgical biopsy showed circumferential cellular crescents, multinucleated giant cells, and exudation of fibrin in all glomeruli. Immunofluorescence microscopy demonstrated deposition of immunoglobulin G, C3, and membrane attack complex along glomerular capillary walls. Multinucleated giant cells were suggested to be macrophage-monocyte lineage because they were CD68 positive. Bone marrow aspiration showed an increase of plasma cells. Immunostaining showed intensive expression of interleukin-6 (IL-6) in practically every part of the renal sites involving multinucleated cells, crescents, tubules, and infiltrating cells, suggesting that one of the sources of systemically elevated IL-6 was the kidney. Serum IL-6, anti-glomerular basement membrane antibody, and acute-phase proteins were markedly elevated, and returned dramatically to the normal level after corticosteroid therapy and plasmapheresis. We believe that IL-6 played an important role in the development of many symptoms in the present case.
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PMID:Pathogenic significance of interleukin-6 in a patient with antiglomerular basement membrane antibody-induced glomerulonephritis with multinucleated giant cells. 761 Dec 72

Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD.
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PMID:Aleutian mink disease: puzzles and paradigms. 788 16

The use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to abrogate chemotherapy-induced neutropenia has become a routine part of many cancer treatment regimes. However, there are still very few data available about possible complications related to repeated or prolonged use of these agents in patients with malignant solid tumors. The authors report a child with brainstem glioma who received repeated cycles of multiagent chemotherapy with G- or GM-CSF support. During this period of 10 months, no clinical side effects were observed that could have been attributed to growth factor administration. However, postmortem histological examination revealed the presence of diffuse plasmacytosis, a rare hematological disorder in childhood. Undifferentiated plasma cells of nonmonoclonal origin could be demonstrated infiltrating bone marrow, lungs, and lymph nodes of the patient. Based on previously published in vitro and in vivo evidence on the interleukin-6 (IL-6)-mediated stimulatory effect of G- and GM-CSF on myeloma cell proliferation, the authors suggest a possible link between extensive growth factor support and the development of plasmacytosis in this patient.
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PMID:Diffuse plasmacytosis in a child with brainstem glioma following multiagent chemotherapy and intensive growth factor support. 861 71


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