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)

We report the case of a 33-year-old Japanese male who presented with thrombocytosis, lower limb edema, severe polyneuropathy with elevated cerebrospinal fluid (CSF) protein level and serum IgA lambda monoclonal component, fulfilling the manifestations of Crow-Fukase syndrome. A high level of soluble interleukin-6 receptor in the CSF was also found, which fluctuated in parallel with the clinical course. Initial treatment with double-filtration plasmapheresis (DFPP) reduced the serum IgA paraprotein level with improvement of the sensory component of the polyneuropathy and decrease of soluble interleukin-6 receptor in the CSF. The remaining clinical features waned off after steroid treatment. The possible role of interleukin-6 in the pathogenesis of the Crow-Fukase syndrome and the utility of DFPP treatment are discussed.
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PMID:A case of Crow-Fukase syndrome with elevated soluble interleukin-6 receptor in cerebrospinal fluid. Response to double-filtration plasmapheresis and corticosteroids. 748 19

We describe a case of cyclic thrombocytopenia and thrombocytosis, whose cytokine levels, granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-6 (IL-6) in plasma, fluctuated in synchrony with platelet count. The levels of the two cytokines correlated significantly with the platelet count for 11 observations over an 8-month period (r = 0.79, p < 0.01 for GM-CSF and r = 0.87, p < 0.001 for IL-6). No inverse relationship between platelet-associated immunoglobulin G (PAIgG) and platelet count was observed (r = 0.39, p > 0.20). These findings suggest that the fluctuation of platelet count in this case may result from an aberration of the cytokine network regulating megakaryopoiesis and platelet formation.
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PMID:Synchronous fluctuation of interleukin-6 and platelet count in cyclic thrombocytopenia and thrombocytosis. 749 73

Interleukin-6 plays an important role in host defense mechanisms and it appears to be a major mediator of the acute-phase response. IL-6 is also an important thrombocytopoietic factor. High serum levels of IL-6 are present in reactive thrombocytosis. The number and function of circulating platelets are the major factors that affect megakaryocytopoiesis by thrombopoietin. High levels of thrombopoietin have been observed in patients with thrombocytopenic purpura. To evaluate a possible thrombopoietin-like function of IL-6, we measured IL-6 levels in the serum of patients affected by post-infective acute thrombocytopenic purpura using a sensitive ELISSA assay. As controls, we studied normal subjects and patients with reactive thrombocytosis. No significant difference was observed between thrombocytopenic patients and normal controls. High IL-6 levels were present in patients with reactive thrombocytosis. In conclusion, we had not observed high levels of IL-6 in acute thrombocytopenic purpura and, very probably, IL-6 is not involved in the regulation of platelet mass for the hemostatic function. The thrombocytopoietic activity of IL-6 is another acute-phase response and it is consistent with the other functions of this cytokine. This suggests an active participation of platelets in host defense mechanisms.
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PMID:Low serum levels of interleukin-6 in children with post-infective acute thrombocytopenic purpura. 762 86

A role for interleukin-6 (IL-6) in malignant mesothelioma has been suggested by the clinically presenting symptoms of mesothelioma patients, which include fever, weight loss and thrombocytosis. A murine model of malignant mesothelioma was therefore used to examine the potential role of IL-6 in this cancer type and whether the effect of interferon alpha (IFN alpha) therapy on mesothelioma might be mediated, in part, by regulating IL-6 levels and/or IL-6-induced pathobiology. A panel of human and murine mesothelioma cell lines was assayed for endogenous IL-6 production in a bioassay, and for IL-6-mRNA expression. Four out of 5 human and 5 out of 15 murine mesothelioma cell lines produced moderate to high levels of bioactive IL-6 in vitro. This result was corroborated by mRNA detection. One of the representative murine cell lines, AB22, was chosen for further in vivo studies in the murine mesothelioma model. In AB22-inoculated mice detectable serum IL-6 levels were found to precede macroscopically detectable tumour growth, clinical signs (cachexia, abdominal distension, diarrhoea) and changes in the peripheral lymphoid organs (cell depletion and functional depression). Treatment with anti-IL-6 antibody curtailed the clinical symptoms (P < 0.001), as did treatment with recombinant human (rhu) IFN alpha (P < 0.001). Neither anti-IL-6 antibody nor rhuIFN alpha had a direct growth-inhibitory effect on the AB22 mesothelioma cell line in vitro, however, in vivo rhuIFN alpha treatment of mice inoculated with AB22 cells attenuated both IL-6 mRNA expression in the tumours and serum IL-6 levels, ameliorated the depression of lymphocyte activities, and enhanced the number of tumour-infiltrating lymphocytes and macrophages. On the basis of these results it is suggested that IL-6 mediates some of these effects, directly or indirectly, and that a combination therapy of rhuIFN alpha and anti-IL-6 antibody may be an improved palliative treatment for patients with malignant mesothelioma.
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PMID:Interleukin-6 involvement in mesothelioma pathobiology: inhibition by interferon alpha immunotherapy. 775 Jan 22

Traditional diagnostic criteria for primary thrombocythaemia (PT) remain essentially negative, aiming to exclude other myeloproliferative disorders and causes of reactive thrombocytosis (RT). It would be useful to have positive markers. We have examined several parameters to see how well they discriminate between PT and RT. Three groups of patients were studied: new, untreated PT (17), treated PT (12) and RT (17). Data consisted of: ESR, plasma fibrinogen, factor VIIIC, von Willebrand factor antigen (vWF:Ag), PDW, platelet nucleotide ratio (ATP:ADP) serum erythropoietin (Epo), ristocetin cofactor (vWF:RiCoF), multimeric structure of vWF, interleukin-6, evidence of clinical ischaemia and erythroid colony formation. Erythroid colonies were assayed in a serum-free system with the addition of Epo, IL3 or alpha-IFN to produce a discriminant function (DF) successfully used in the diagnosis of primary polycythaemia in an earlier study. Acute phase reactants (ESR, fibrinogen, VIIIC, vWF:Ag) and IL6 were the best discriminants, while PDW and serum Epo were less so. ATP:ADP and clinical ischaemia were nondiscriminatory in this study. Reduction in vWF:RiCof and in high molecular weight multimers were clearly associated with PT. Endogenous erythroid colonies were nondiscriminatory, but half the PT group and only one patient in the RT group obtained a DF suggestive of myeloproliferative disorder. Judicious use of a battery of tests may provide support for diagnosis of PT in difficult cases.
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PMID:Primary thrombocythaemia: a composite approach to diagnosis. 795 22

The ability of interleukin-6 (IL-6) to modulate immune parameters and mesangial cell function suggests a role for this cytokine in the development of autoimmune glomerulonephritis. This hypothesis was tested in 6-month-old female (NZB x NZW)F1 mice that were administered recombinant human IL-6 (rhIL-6) (50 and 250 micrograms/kg s.c.) for 12 weeks, resulting in an accelerated and severe form of membranoproliferative glomerulonephritis associated with marked upregulation of mesangial major histocompatibility complex class II antigen and glomerular ICAM-1 expression. To distinguish direct effects of rhIL-6 on the renal mesangium from those mediated through the immune system, (NZB x NZW)F1 mice were immunosuppressed with cyclosporin. Immunosuppression by cyclosporin inhibited the development of glomerulonephritis, decreased class II antigen expression, and abrogated IL-6-mediated effects. Administration of neutralizing anti-IL-6 antibody had no effect on the spontaneous development of glomerulonephritis in (NZB x NZW)F1 mice. This finding, together with undetectable IL-6 serum levels, makes a pathogenetic role of endogenously produced IL-6 in this disease model unlikely. In contrast to (NZB x NZW)F1 mice, parental NZW or BALB/c mice given high doses of rhIL-6 (500 micrograms/kg) or recombinant murine IL-6 (100 micrograms/kg) daily for 4 weeks failed to develop morphological or biochemical evidence of glomerulonephritis. Induction of acute phase proteins, anemia, thrombocytosis, and induction of renal class II antigen confirmed the biological activity of IL-6 in these mice. In conclusion, while non-nephritogenic in normal mice, IL-6 accelerates the development of the genetically determined glomerulonephritis of (NZB x NZW)F1 mice through effects mediated by a modulated immune system. Since neutralizing IL-6 antibody treatment did not prevent the development of glomerulonephritis, it is unlikely that increased IL-6 production plays a role in the pathogenesis of lupus nephritis.
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PMID:Interleukin-6 exacerbates glomerulonephritis in (NZB x NZW)F1 mice. 817 44

Thrombocytosis and fever are frequent symptoms in children with hepatoblastoma. Interleukin-6 (IL-6) has been shown to mediate thrombocytosis and an acute-phase reaction including fever. We therefore investigated samples from 14 untreated patients with hepatoblastoma for this cytokine and in addition for interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), all of which are known to induce IL-6 production. High serum levels of IL-6 were only found in 3/14 patients; the other cytokines were not detectable. In contrast, 12/14 tumors produced substantial amounts of IL-6 in primary cell culture, while IL-1 beta was found in 3/14 supernatants; IL-1 alpha and TNF-alpha were always negative. Immunoenzymatic staining of fresh tumors revealed that IL-6 is not produced by the tumor cells, but rather by surrounding fibroblasts and endothelial cells. In tumor cells only IL-1 beta, but neither IL-1 alpha, TNF-alpha nor IL-6, could be detected. In co-culture experiments with fibroblasts and endothelial cells, addition of hepatoblastoma cells enhanced IL-6 production. Including an IL-1 receptor antagonist abolished this effect incompletely. Our results suggest that tumor cells in hepatoblastoma induce IL-6 production in surrounding fibroblasts and endothelial cells by virtue of their endogenous secretion of IL-1 beta and supposedly some other, as yet unidentified, mediator.
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PMID:Production of interleukin-1 beta and interleukin-6 in hepatoblastoma. 838 28

In humans and nonhuman primates, the in vivo administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) consistently results in marked increase of megakaryocyte ploidy and size similar to that observed with interleukin-6 (IL-6). However, whereas the administration of IL-6 also results in an increase in circulating platelets, there is no predictable corresponding increase in peripheral blood platelets following treatment with rhGM-CSF. To determine whether the failure of rhGM-CSF to produce thrombocytosis is secondary to cytokine-related increased platelet activation and consumption in vivo, we quantified autologous platelet survival time and in vivo platelet activation before and during 5 days of administration of rhGM-CSF to two rhesus monkeys. Platelet survival was measured using autologous platelets labeled with 111Indium-oxine. Platelet activation was assessed by flow cytometric determination of the expression of the major platelet membrane glycoprotein (GP) IIb/IIIa complex, and an activation-dependent epitope on GPIIb/IIIa (recognized by monoclonal antibodies [MABs] LJ-P4 and PAC1, respectively). Platelet activation was also assessed by dose-response aggregometry using adenosine diphosphate (ADP). While megakaryocyte ploidy increased during rhGM-CSF administration, peripheral platelet counts were 418 x 10(9)/L and 525 x 10(9)/L before and 402 x 10(9)/L and 508 x 10(9)/L during cytokine treatment in animals 1 and 2, respectively. No changes were observed in the mean platelet volume. 111Indium-labeled platelet recovery in circulation was similar before (94.7%, 91.8%) and during (92.9%, 92.8%) rhGM-CSF administration, which indicates that cytokine-related in vivo sequestration of platelets does not occur. Autologous platelet survival was 5.6 and 6.2 days before and 5.0 and 5.4 days during the rhGM-CSF treatment (p = 0.07), without significant change in the corresponding platelet turnover rate (derived from the platelet count and survival time). The flow cytometric analysis showed no increase in the binding of either LJ-P4 or PAC1 MABs to the platelet membrane during rhGM-CSF administration. The aggregometry studies demonstrated similar concentrations of ADP inducing half-maximal aggregation (ED50). Overall, the above data indicate that treatment with rhGM-CSF is not associated with in vivo activation, sequestration, or increased consumption of platelets. The data suggest that the failure of rhGM-CSF-stimulated megakaryocytes to increase peripheral platelet count is a manifestation of ineffective megakaryocytopoiesis resulting from inability to increase platelet delivery to the circulation.
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PMID:Effects of recombinant human granulocyte-macrophage colony-stimulating factor on platelet survival and activation using a nonhuman primate model. 840 39

A mesothelioma cell line, termed T-85, was established from a patient with malignant peritoneal mesothelioma and remarkable thrombocytosis (1.4 x 10(6)/mm3). Electron microscopically, two types of mesothelioma cells have been characterized; the major type of cells with dense-cored granules in the cytoplasm and the minor one with evenly dense granules. Immunologically, the cells showed staining for interleukin-6 (IL-6), cytokeratin, collagen type IV, vimentin, laminin, fibronectin and Factor VIII-related antigen. Quantitation by ELISA revealed a high concentration of IL-6 in T-85 cell culture supernatants. RT-polymerase chain reaction of T-85 cells showed two positive bands of cDNA at 628 and 251 base pairs indicating the constitutive expression of IL-6 and IL-6 receptor mRNA. Moreover, prominent pro-platelet process formation activity in T-85 cell culture supernatants indicated the presence of a thrombopoietic activity due mainly to IL-6 but not the c-Mpl ligand or erythropoietin. However, the fact that 15% of PPF activity remained in the supernatants treated with anti-IL-6 antibody indicated the presence of another thrombopoietic substance. T-85 is so far the first mesothelioma cell line derived from a case with remarkable thrombocytosis.
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PMID:Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis. 887 1

Chronically elevated serum levels of proinflammatory cytokines is a feature of the syndrome known as POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes). A patient had a POEMS syndrome with thrombocytosis and biclonal gammopathy and was treated as follows: all-trans-retinoic acid (tretinoin) at 90 mg/day for 50 days, no treatment for 70 days, readministration of tretinoin at 75 mg/day for 180 days. Focal bone lesion irradiation was performed from day 26 to day 50. Serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), and IL-1 beta normalized within 7 days after the first administration of tretinoin, transiently increased at the time of radiotherapy, increased again after withdrawal of the tretinoin, and decreased again after its reintroduction. The platelet count and gammopathy paralleled the changes in the cytokine levels. This study documents in vivo the ability of all-trans-retinoic acid to down-regulate the release of IL-6, IL-1 beta, and TNF alpha, and illustrates its potential as a therapeutic agent in conditions associated with chronic overproduction of proinflammatory cytokines.
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PMID:All-trans-retinoic acid in POEMS syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines. 870 54


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