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)

Castleman's disease (CD) is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes. CD may be localized or multifocal, and is often associated with signs and symptoms of generalized inflammation. The systemic manifestations of CD have been previously attributed to an overproduction of interleukin-6 (IL-6) by the tumor, although there is evidence that IL-6 is not responsible for all of the symptoms. We describe a 9-year-old boy who developed Castleman's disease with systemic findings of hypochromic microcytic anemia, growth arrest, inflammation, and hyperimmunoglobulinemia. Following surgical resection, all of the symptoms and laboratory abnormalities resolved. Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis of the tumor, we found elevated levels of IL-6 mRNA as expected, but also elevated levels of tumor necrosis factor beta (TNF-beta) and gamma interferon (gamma-IFN) mRNA. Because these cytokines are mediators of immune regulation and inflammation, we propose that TNF-beta and gamma-IFN also play an important role in the pathophysiology of Castleman's disease.
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PMID:Elevated levels of tumor necrosis factor-beta, gamma-interferon, and IL-6 mRNA in Castleman's disease. 749 11

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.
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PMID:Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. 863 55

A patient is presented who had Castleman's disease with constitutional symptoms, a palpable supraclavicular/ axillar mass, and a microcytic anemia, among other laboratory abnormalities, including elevated levels of interleukin-6. Treatment consisted of irradiation of the involved area, with subsequent disappearance of all symptoms and normalization of the laboratory abnormalities. Iron kinetic studies demonstrated a hypoproliferative erythropoiesis, which normalized after radiotherapy. Hypoproliferative erythopoiesis could not be ascribed to serum inhibitors, since normal burst-forming units were observed in the absence or presence of autologous serum. The role of interleukin-6 in relation to Castleman's disease is highlighted.
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PMID:A case of localized Castleman's disease with systemic involvement: treatment and pathogenetic aspects. 869 26

Interleukin-6 (IL-6) is a 4-helical protein that binds to a specific IL-6 receptor on target cells and to two molecules of the promiscuous signal transducing protein, glycoprotein 130 (gp130). Structure-function analysis has led to the definition of molecular contacts between IL-6 and its receptor subunits. This knowledge has led to the design of competitive antagonistic proteins that retain their receptor binding capability, but fail to stimulate one or both gp130 proteins; the properties of such recombinant antagonistic proteins are compared with traditional neutralising monoclonal antibodies targeted at IL-6 or receptor subunits. Furthermore, several strategies have been employed to construct molecules with increased bioactivity. Possible therapeutic applications in putative IL-6 dependent haematologic disorders, e.g., Castleman's disease (CD), POEMS syndrome, multiple myeloma, and bone diseases, e.g., Paget's disease, osteoporosis, are outlined. IL-6 antagonists could also, in theory, suppress inflammatory activity in rheumatic and autoimmune diseases and could prevent secondary amyloidosis. This principle may prove advantageous in myocardial infarction (MI) and unstable angina pectoris. More generally, IL-6 antagonists could improve the wasting and microcytic anaemia of chronic diseases. IL-6 antagonists might slow down development of mesangio-proliferative glomerulonephritis (MPGN). Hyperagonistic variants of IL-6 have a potential use in the ex vivo expansion of haematopoietic progenitor cells and as thrombopoietic agents. They might well be the first drugs to aid liver regeneration in vivo.
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PMID:The therapeutic potential of interleukin-6 hyperagonists and antagonists. 1598 26

Chordoid meningioma is a rare meningothelial tumor characterized by chordoma-like histological features with lymphoplasmacellular infiltration. This tumor is often seen in children, but not in adults, with a systemic inflammatory syndrome (iron-resistant microcytic anemia and/or dysgammaglobulinemia) and very rarely with a persistent moderate hyperthermia. In the present report the authors describe a temporal chordoid meningioma in a 30-year-old woman who presented with fever, headache, and a serological inflammatory syndrome. The clinical symptomatology, chiefly the fever, disappeared immediately after removal of the tumor. To the authors' knowledge, only one similar patient with such clinical presentation and response to surgery has been mentioned in the literature. Interestingly, at immunohistochemical examination, the neoplasm showed focal positivity for the pyrogenic cytokine interleukin-6. The capacity of the tumor to produce this pyrogenic cytokine could explain both the patient's clinical presentation and her response to the surgical management.
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PMID:Pyrogenic cytokine interleukin-6 expression by a chordoid meningioma in an adult with a systemic inflammatory syndrome. Case report and review of the literature. 1623 90

Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD.
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PMID:Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway? 1854 42

Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].
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PMID:Castleman-Kojima disease (TAFRO syndrome) : a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly : a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012). 2380 Nov 35

Emerging evidence suggests that chronic exposure to DDT and its derivatives is associated with a variety of human disorders such as anemia. The present study demonstrated that p,p'-DDT caused microcystic anemia in a dose-dependent manner (0, 5, 50, and 500 ppm) in the long-term study up to 2 years. To elucidate the mechanism(s) by which p,p'-DDT induces anemia, certain hematological parameters were assessed in rats fed specific doses of p,p'-DDT for 2 weeks, and the effect of lipopolysaccharide on anemia of inflammation was also examined in p,p'-DDT-treated rats. The parameters included the content of hemoglobin per reticulocyte, mean corpuscular volume of reticulocytes and mature erythrocytes, corpuscular hemoglobin concentration mean of mature erythrocytes, and saturation levels of transferrin and iron. During the 2-week treatment period, hypochromic microcytic reticulocytes and hypochromic normocytic mature erythrocytes were observed in p,p'-DDT-treated rats, with no evidence of alteration in plasma iron levels. p,p'-DDT enhanced microcytosis of reticulocytes, as well as mature erythrocytes, which occurred due to severe hypoferremia resulting from anemia of inflammation; however, plasma iron levels were attenuated probably through the inhibition of interleukin-6. Our data suggests that long-term treatment with p,p'-DDT induces microcytic anemia, possibly because of the impairment of iron utility in erythrocytes.
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PMID:p,p'-DDT induces microcytic anemia in rats. 2406 25

Chronic, iron-refractory, microcytic anemia can be a diagnostic and therapeutic challenge. We report the cases of 2 children with occult, unicentric Castleman disease whose primary presenting feature was a chronic, unexplained, iron-refractory, microcytic anemia. Diagnosis was delayed because neither child had palpable lymphadenopathy and the lymphoproliferation was intra-abdominal. Surgical resection cured the anemia and the Castleman disease. A diagnostic clue to Castleman disease is an elevated concentration of interleukin-6 in blood, which causes anemia by inducing the expression of the iron-regulatory hormone hepcidin.
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PMID:Iron-refractory microcytic anemia as the presenting feature of unicentric Castleman disease in children. 2436 88