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)

Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP.
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PMID:[Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura]. 192 Aug 40

We investigated the effect of high-dose intravenous gamma globulin therapy on the plasma level of macrophage-colony stimulating factor (M-CSF) level in 13 patients with chronic idiopathic thrombocytopenic purpura. M-CSF and interleukin-6 levels were determined by enzyme-linked immunosorbent assay. The mean +/- S.D. level of M-CSF in the patients was 1235 +/- 439 U/ml, and the level in 8 patients was higher than the mean + S.D. (903.6 U/ml) in normal controls. All 8 patients had steroid-refractory disease. M-CSF levels were significantly correlated with the serum levels of interleukin-6 (r = 0.66, P < 0.05). Interleukin-6 levels were also significantly raised in the high M-CSF group compared with the normal M-CSF group (P < 0.05). In the whole patient population, M-CSF levels decreased, but not significantly, after intravenous gamma globulin, while interleukin-6 decreased significantly. However, in the patients with high pretreatment M-CSF levels, both M-CSF and interleukin-6 decreased significantly after treatment (M-CSF, 4 weeks, P < 0.05; IL-6, 1 week, P < 0.05, 4 weeks, P < 0.01). These findings suggest that high-dose intravenous gamma globulin causes thrombocytosis by the decrease of M-CSF levels in idiopathic thrombocytopenic purpura.
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PMID:High-dose intravenous gamma globulin reduces macrophage colony-stimulating factor levels in idiopathic thrombocytopenic purpura. 893 36

Agnogenic myeloid metaplasia (AMM) is a disease characterized by bone marrow megakaryocyte hyperplasia and clusters of megakaryocytes, in which many of the megakaryocytes are atypical. In order to elucidate the mechanisms of megakaryocytosis, ELISA assays of blood levels of thrombopoietin (TPO), interleukin-6 (IL-6) and interleukin-11 (IL-11) were done in 45 patients with AMM and compared with normal volunteer controls. Higher blood TPO levels were found in AMM than in controls (P < 0.0001), and blood TPO levels were correlated with the degree of marrow fibrosis (P = 0.0078). Blood levels of IL-6 were also significantly higher in AMM, when compared with controls (P < 0.0001). However, no correlation was found between blood IL-6 levels and degree of marrow fibrosis. No correlation was found between either TPO or IL-6 and the number of blood platelet counts, the number of marrow megakaryocytes, WBC counts, or the degree of splenomegaly. Blood IL-11 levels were undetectable in most patients and no significant difference was found in AMM as compared to controls. The present study demonstrated that, while in idiopathic thrombocytopenic purpura (ITP) or aplastic anemia, blood TPO levels are relatively correlated with the numbers of platelet and/or megakaryocyte mass, blood TPO levels do not correlate with blood platelet counts, or marrow megakaryocyte mass in AMM. Therefore, in AMM, other mechanisms such as the number of TPO receptors on platelets or megakaryocytes, c-MPL receptor abnormalities, abnormal production of TPO mRNA and so on, will have to be studied. Furthermore, TPO may play a significant role in the pathogenesis of marrow fibrosis; IL-6 may be a factor in the development of marrow megakaryocytosis but its elevated blood levels may represent a secondary immune phenomenon; and IL-11 probably does not play a significant role in causing marrow megakaryocytosis in this disease.
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PMID:Blood thrombopoietin, IL-6 and IL-11 levels in patients with agnogenic myeloid metaplasia. 936 14

'Stress thrombocytes', i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = -0.32, p = 0.019) and IL-6 (r = -0. 41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented 'residual platelet' functions in ITP.
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PMID:Selectins and IL-6 during the clinical course of idiopathic thrombocytopenic purpura. 1008 33

The utility of isotachophoresis-capillary zone electrophoresis (ITP-CZE) and high-performance size-exclusion chromatography (HPSEC) was investigated for determination of dimeric and monomeric recombinant human interleukin-6 (rhIL-6). Using ITP-CZE heterogeneity of dimeric rhIL-6 could be revealed resolving two peaks in the electropherograms, while with HPSEC dimeric rhIL-6 eluted as one homogeneous fraction. Both protein forms were monitored during incubation of monomeric rhIL-6 at different pH and temperature. The selectivity of counterflow ITP-CZE in conjunction with the low concentration determination limits enabled reanalysis of HPSEC fractions for identification of the dimer in the electropherograms. Both ITP-CZE and HPSEC were shown to be suitable to monitor the dimerization of rhIL-6, similar monomer-to-dimer peak area ratios were obtained throughout the incubation. Dimer formation kinetics increased with decreasing pH and with increasing temperature, it was entirely suppressed at neutral pH and room temperature. In contrast to HPSEC, ITP-CZE enabled separation of further still unidentified artifacts apparently formed during incubation of rhIL-6. CZE analysis in conjunction with electrospray ionization mass spectrometry revealed the non-covalent binding character of the dimeric rhIL-6 complex and facilitated interpretation of the electropherograms.
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PMID:Utility of isotachophoresis-capillary zone electrophoresis, mass spectrometry and high-performance size-exclusion chromatography for monitoring of interleukin-6 dimer formation. 1036 Mar 28

InKine Pharmaceutical Co. is developing an oral compound, CBP 1011, for the treatment of immune thrombocytopenic purpura (ITP) [Hematrol] and for the treatment of inflammatory bowel disorders, ulcerative colitis and Crohn's disease (Colirest). This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. CBP 1011 or medroxyprogesterone, is a progesterone agonist and inhibits pro-inflammatory mediators such as interleukin-6 and tumour necrosis factor (TNF). CBP 1011 was originally developed by CorBec Pharmaceuticals, which in 1997 was aquired by Panax and then intergrated into InKine Pharmaceuticals. According to a company spokesperson, InKline is pursuing outlicensing opportunities for Hematrol since the company's current commercial focus is on gastrointestinal products. In June 2000, InKine announced the completion of a study comparing the bioavailability of a commercially viable tablet formulation of CBP 1011 to the original capsule formulation that is currently being used in the company's phase III studies in patients with idiopathic thrombocytopenic purpura. Preliminary results from this study indicate that the bioavailability of the tablet formulation does not differ significantly from that of the capsule formulation. The trial enrolled ITP patients (i) who are HIV positive, (ii) who are chronic ITP sufferers despite having had a splenectomy, (iii) who are older, or (iv) who have less severe thrombocytopenia. In preclinical trials, CBP 1011 was shown to decrease lymphocyte infiltration into the bowel compared with the control. Studies also show that it possibly offers safety benefits over steroid therapies. In June 2001, InKine commenced enrolment for a pivotal phase III trial in the treatment of Crohn's disease. This randomised, double-blind trial will enrol approximately 250 patients and will compare two doses of CBP 1011 (400 and 1000mg) with placebo. In April 2003, the US Patent and Trademark Office granted InKine Pharmaceutical a 'Notice of Allowance' for the 'Method of Treating Inflammatory Conditions with Progesterone or Progesterone Analogs'. This patent for medroxyprogesterone (Colirest) provides InKine patent protection for the use of Colirest in treating patients with Crohn's disease, ulcerative colitis, proctitis, microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, drug-induced oesophagitis, coeliac disease, recurrent polyps and haemorrhoids. The patent protection also covers Colirest in a variety of delivery forms such as tablet, enema, suppository, foam, gel, ointment and suspension.
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PMID:CBP 1011: Colirest, Hematrol. 1284 89

Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by beta-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor alpha, interleukin-6, interleukin-10 and transforming growth factor beta(1) (TGF-beta(1)) in the tissue. NF-B expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor alpha and interleukin-6, as well as TGF-beta(1) mRNA, were increased. In addition, the NF-B expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-beta(1) mRNA. Thus, exercise training in a model of beta-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance.
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PMID:Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained beta-adrenergic hyperactivity. 2063 82