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)

Changes in peripheral blood platelet counts associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing, in each patient, the value obtained on the day thalidomide therapy commenced with the average of the three preceding values. In the 11 patients studied, the mean platelet count rose from 235 to 322 x 10(3)/mm3, p < 0.001. In 3, the platelet count was above the normal limit, qualifying as thrombocytosis, in 7 the rise was appreciable, and in 2 it was negligible. In the 3 patients studied 1-2 weeks after beginning thalidomide, the mean count was 414 x 10(3)/mm3. Counts obtained after 3 or more weeks of thalidomide therapy were within normal limits. This study provided no direct evidence as to the mechanism responsible for the elevated platelet count, but mediation by interleukin-6 (IL-6) was concluded to be an attractive hypothesis, consistent with prior studies of IL-6 in reactive thrombocytosis and of IL-6 in ENL.
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PMID:Elevated platelet counts and thrombocytosis in erythema nodosum leprosum. 1248 64

Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis and physiopathology of various chronic inflammatory conditions including Crohn's disease (CD). Among these cytokines, interleukin-6 (IL-6) must be especially important because increased serum concentrations of acute phase proteins, reduced level of serum albumin, and remarkable thrombocytosis are all well-explained by the increased level of IL-6. Moreover, IL-6 is capable of stimulating even IL-6 receptor (IL-6R) negative cells such as vascular endothelial cells when complexed to soluble form of IL-6R (sIL-6R), and serum level of IL-6 as well as sIL-6R has been demonstrated to increase during inflammation. To investigate the therapeutic potential of IL-6 signaling blockade for CD, anti-IL-6R monoclonal antibody (mAb) was introduced to various murine models of colitis. Anti-IL-6R mAb successfully prevented wasting disease and the development of macroscopic and histological lesions. It suppressed the accumulation of ICAM-1 positive and Mac-1 positive cells in the lamina propria (LP) and the expression of ICAM-1 and VCAM-1 by vascular endothelial cells. Expansion of colonic and splenic CD4(+) T cells was reduced as well as the colonic expression of tumor necrosis factor alpha (TNF-alpha), IL-1beta, and interferon gamma (IFN-gamma) mRNA without affecting the production of transforming growth factor beta (TGF-beta), IL-10, and IL-4 mRNA. The treatment also suppressed established colitis by inducing LP T cell apoptosis. These results strongly suggest that specific targeting of IL-6/sIL-6R pathway will be a promising new approach for the treatment of CD, and the clinical trial of humanized anti-IL-6R mAb is now under way.
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PMID:Anti-interleukin-6 therapy for Crohn's disease. 1257 Aug 22

Thrombopoietin (TPO) is the major regulator of platelet production. Plasma levels of TPO are thought to be regulated by its binding to platelets and megakaryocytes. Here we have used a model of cardiac surgery with cardiopulmonary bypass (CBP) to test the possibility that changes in TPO levels are influenced by the presence of coronary artery disease (CAD) and by changes in interleukin-6 (IL-6). After surgery patients with CAD (n = 22) or with normal coronary arteries (n = 11) showed a significant thrombocytopaenia followed by a reactive thrombocytosis. The platelet recovery was preceded by a significant rise in TPO (from 62.6 +/- 9.4 pg/ml at baseline to 129.2 +/- 19 pg/ml at 60 h, P <0.001), which in turn was preceded by, and was positively correlated with, a marked increase in circulating IL-6 (from 1.5 +/- 0.3 pg/ml at baseline to 269.3 +/- 30.6 pg/ml at 3-12 h, P <0.001). The rise of both IL-6 and TPO was significantly larger in patients with CAD. No correlation was found between the post-operative drop in platelet mass and changes in either the TPO or IL-6 levels. These findings suggest that in man circulating TPO levels, besides being controlled by changes in platelet mass, are influenced by inflammatory processes, including the presence of coronary atherosclerosis.
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PMID:Rise of circulating thrombopoietin following cardiothoracic surgery is potentiated in patients with coronary atherosclerosis: correlation with a preceding increase in levels of interleukin-6. 1262 39

Transgenic mice carrying human IL-6 cDNA fused with a murine major histocompatibility class-I promoter (H-2L(d)) were serially administered with anti-interleukin-6 receptor (IL-6R) monoclonal antibody (mAb), MR16-1, from the age of 4 weeks to estimate its efficacy on a variety of disorders developed in these mice, most of which are similar to the disorders associated with Castleman's disease. In the control mice treated with isotype-matched mAb, a massive and multiple IgG1 plasmacytosis, mesangial proliferative glomerulonephritis, leukocytosis, thrombocytosis, anemia and abnormalities of blood chemical parameters have developed in accordance with the elevation of serum IL-6, and 50% of mice have died of renal failure by 18 weeks of age. In contrast, the treatment with MR16-1 prevented all these symptoms and prolonged the lifetime of the majority of the mice. Thus, the constitutive overexpression of IL-6 caused various disorders, and the treatment with anti-IL-6R mAb completely prevented from these symptoms. These results clearly confirm that IL-6 indeed plays an essential role in the pathogenesis of a variety of disorders. Furthermore, anti-IL-6R mAb could provide novel therapy for Castleman's disease and MR16-1 should be a useful tool to estimate therapeutic potential of IL-6 antagonists in a variety of murine models for human disease.
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PMID:Anti-interleukin 6 (IL-6) receptor antibody suppresses Castleman's disease like symptoms emerged in IL-6 transgenic mice. 1263 73

Pheochromocytomas are tumors able to produce catecholamines and a variety of biologically active neuropeptides. We report the case of a 36-yr-old female patient with pheochromocytoma exhibiting headache, intermittent fever, thrombocytosis, and marked inflammatory signs. Nonsteroidal anti-inflammatory drugs were ineffective in lowering the body temperature, while a corticosteroid agent obtained excellent results. IL-6 was found elevated (20 pg/ml); it fell to 4.5 pg/ml 3 weeks after the adrenalectomy, in parallel to normalization of other laboratory data. The interleukin-6 (IL-6) over-production can either be ascribed directly to the tumor (as confirmed by immunohistochemistry) or indirectly accounted for by tumoral production, as a consequence of the high levels of circulating norepinephrine. To our knowledge, our paper represents the 6th case report of IL-6 secreting pheochromocytoma associated with clinical markers of inflammatory response.
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PMID:Interleukin-6 producing pheochromocytoma presenting with acute inflammatory syndrome. 1290 74

An autopsy case of granulocyte colony-stimulating factor (G-CSF)- and interleukin-6 (IL-6)-producing diffuse deciduoid peritoneal mesothelioma is reported. The patient was a 70-year-old man with abdominal distension and weight loss in the year prior to his death. Laboratory data suggested severe inflammation with marked leukocytosis, thrombocytosis and elevated serum levels of C-reactive protein, G-CSF and IL-6. Imaging studies showed an expansive mass occupying the entire abdomen and pelvic cavity. Histological diagnosis of tissue taken by needle biopsy was difficult due to the unusual sarcomatoid-appearance of the tumor. In addition, there was severe infiltration of numerous neutrophilic leukocytes. An autopsy revealed that the diffuse peritoneal tumor had a fresh fishmeat-like appearance with focal mucinous degeneration and entirely encased the abdominal organs. Histological examination showed a sheet-like proliferation of tumor cells with large ovoid or polygonal cytoplasm, large atypical nuclei and obvious nucleoli. The tumor cells showed abundant glycogen and hyaluronic acid, and were immunoreactive to cytokeratin, calretinin, epithelial membrane antigen (EMA), CA-125, and focally to vimentin. The tumor cells were immunoreactive to G-CSF and IL-6. Electron microscopy revealed long, slender microvilli on the tumor cell surface. This tumor was diagnosed as a G-CSF- and IL-6-producing, diffuse deciduoid mesothelioma. We report this case with special reference to the differential diagnosis of deciduoid peritoneal mesothelioma with paraneoplastic syndrome.
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PMID:Granulocyte-colony stimulating factor- and interleukin 6-producing diffuse deciduoid peritoneal mesothelioma. 1530 18

The interleukin-6 (IL-6) cytokine family plays an important role in regulating cellular responses during hematopoiesis. We report here that mice homozygous for a knock-in mutation in the IL-6 cytokine family receptor signaling subunit glycoprotein (gp) 130 (gp130(Y757F/Y757F)) that leads to gp130-dependent signal transducers and activators of transcription (STAT) 1/3 hyperactivation develop a broad spectrum of hematopoietic abnormalities, including splenomegaly, lymphadenopathy, and thrombocytosis. To determine whether STAT3 hyperactivation was responsible for the perturbed hematopoiesis in gp130(Y757F/Y757F) mice, we generated gp130(Y757F/Y757F) mice on a Stat3 heterozygous (Stat3(+/-)) background to specifically reduce gp130-dependent activation of STAT3, but not STAT1. Normal hematopoiesis was observed in gp130(Y757F/Y757F):Stat3(+/-) bone marrow and spleen, with no evidence of the splenomegaly and thrombocytosis displayed by gp130(Y757F/Y757F) mice. The perturbed cellular composition of thymus and lymph nodes in gp130(Y757F/Y757F) mice was also alleviated in gp130(Y757F/Y757F): Stat3(+/-) mice. Furthermore, we show that hematopoietic cells from gp130(Y757F/Y757F) mice exhibited increased survival and proliferation in response to IL-6 family cytokines. Collectively, these data provide genetic evidence that gp130-dependent STAT3 hyperactivation during hematopoiesis has pathological consequences affecting multiple organs, and therefore identify the threshold of STAT3 signaling elicited by IL-6 family cytokines as a critical determinant for hematopoietic homeostasis.
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PMID:The threshold of gp130-dependent STAT3 signaling is critical for normal regulation of hematopoiesis. 1565 55

This is the case study of concurrent cytomegalovirus and respiratory syncytial virus infection in an infant who showed thrombocytosis, liver dysfunction and bronchiolitis. The combination of thrombocytosis with this co-infection is causally related to elevated levels of thrombopoietin and interleukin-6. This study represents the first such case ever recorded.
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PMID:An unusual case of thrombocytosis associated with concurrent cytomegalovirus and respiratory syncytial virus infection in an immunocompetent infant: possible roles of thrombopoietin and interleukin-6. 1623 Feb 13

Thrombocytosis is not a frequent event in myelodysplasia (MDS) and is observed mainly in 5q- syndrome and MDS/myeloproliferative (MPD) overlap syndromes. The pathogenetic mechanism of thrombocytosis in 5q- has not been fully elucidated to-date. Bortezomib is a proteasome inhibitor which seems to be effective in MDS. We present here the first case in the literature with MDS/MPD syndrome, sole 5q- anomaly and thrombocytosis in which bortezomib administration normalized platelet count, produced a major erythroid response, and reduced levels of interleukin-6 (IL-6) and TNF-alpha while increased levels of IL-4 in the bone marrow plasma. The study of such cases will reveal the exact role of bortezomib in the management of MDS/MPD.
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PMID:Bortezomib is an effective agent for MDS/MPD syndrome with 5q- anomaly and thrombocytosis. 1682 Feb 6

A 49-year-old man was admitted with high-grade fever, night sweating and cervical lymphadenopathy in September 2005. On examination, both neutrophilia and thrombocytosis were noted in the peripheral blood, a bone marrow examination revealed marked both myeloid and megakaryocytic hyperplasia. The sera obtained at initial presentation showed an elevated levels of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6). A pathologic diagnosis of T-cell rich B-cell lymphoma was made based on an inguinal lymph node biopsy. Following treatment with CHOP accompanied by rituximab (R-CHOP), both the neutrophilia and thrombocytosis subsided after 3 courses of R-CHOP, resulting in a complete remission after 4 courses of chemotherapy. Neutrophilia, thrombocytosis and T-cell rich B-cell lymphoma in this patient were considerably ameliorated with chemotherapy. We report here a patient with T-cell rich B-cell lymphoma associated with both neutrophilia and thrombocytosis, suggesting that the lymphoma triggered both myeloid and megakaryocytic hyperplasia.
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PMID:[T-cell rich B-cell lymphoma associated with neutrophilia and thrombocytosis]. 1744 79


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