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)

The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is overrepresented in certain patient groups with atherosclerosis or restenosis. We hypothesized and tested whether it may affect cytokine-induced levels of soluble (s) E-selectin, or be associated with proinflammatory or procoagulant properties in a well-standardized inflammation model. Healthy male volunteers (n = 157) received a lipopolysaccharide (LPS) infusion and were genotyped for the S128R SNP, and outcome parameters were measured by enzyme immunoassays and real-time polymerase chain reaction (RT-PCR, Taqman). The S128R SNP had no pronounced effects on basal or inducible sE-selectin levels, or levels of tumor necrosis factor or interleukin-6. However, carriers of the S128R SNP had 20% higher monocyte counts at 24 hours after LPS infusion. Importantly, the S128R allele enhanced thrombin generation by 50% to 80%, as measured by prothrombin fragment F(1+2) (P < .01), and hence fibrin formation (D-dimer) 2-fold (P = .01 to P = .002). However, tissue factor (TF) mRNA levels were not affected. The S128R E-selectin genotype is associated with procoagulant effects in a human model of endotoxin-induced, TF-triggered coagulation. This could contribute to its linkage with various thrombotic cardiovascular disorders.
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PMID:The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia. 1554 47

Interleukin-6 levels, but not prothrombin fragment 1 + 2, correlates with a point-based score for stroke risk in atrial fibrillation, even after oral anticogulation.
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PMID:Relation of interleukin-6 levels and prothrombin fragment 1+2 to a point-based score for stroke risk in atrial fibrillation. 1578 Oct 23

Pentoxifylline (PTX, a methylxanthine derivative) has been found to interrupt early gene activation for tumour necrosis factor, interleukin-1, interleukin-6 and tissue factor production and to improve survival from experimental sepsis. During endotoxaemia, lipopolysaccharide (LPS, endotoxin) and proinflammatory cytokines trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. The present study was undertaken to determine whether pentoxifylline could prevent coagulation disturbances in LPS-treated rabbits. Endotoxaemia was induced with E. coli lipopolysaccharide in New Zealand White rabbits. Forty rabbits were used and divided into four equal groups. Group 1 served as a control group; Group 2: lipopolysaccharide was injected intravenously, Group 3: pentoxifylline was injected intraperitoneally, Group 4: lipopolysaccharide and pentoxifylline were injected simultaneously. Blood samples were collected 6 h after the treatments. In rabbits with endotoxin-induced DIC, platelet count, leukocyte count, percentage of differential leukocyte values, fibrinogen level, antithrombin III (AT-III) and protein C (PC) activity were decreased. Moreover, activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged when compared to the control group. In conclusion, haemostatic disturbances associated with endotoxin-induced DIC were moderately suppressed by the administration of PTX.
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PMID:Effect of pentoxifylline on endotoxin-induced haemostatic disturbances in rabbits. 1615 28

The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p < or = 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.
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PMID:Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis: the Edinburgh Artery Study. 1635 7

We hypothesized that infusion of recombinant human antithrombin without concomitant heparin would have dose-dependent anticoagulant properties and potentially decrease endotoxin (lipopolysaccharide [LPS])-induced cytokine production. This was a randomized, double-blind, placebo-controlled study in parallel groups enrolling 30 healthy male volunteers. The active treatment groups received infusions of recombinant human antithrombin to increase antithrombin levels to 200% and 500% before infusion of 2 ng/kg endotoxin (LPS). Infusion of antithrombin dose-dependently decreased coagulation (P < .01 by repeated-measures ANOVA): peak levels of prothrombin fragment (1.8 nmol/L [95% confidence interval (CI), 1.3-2.3 nmol/L] in the 500% antithrombin group and 4.4 nmol/L [95% CI, 2.7-6.2 nmol/L] in the placebo group at 4 hours), thrombin antithrombin complexes (12 microg/L [95% CI, 8-16 microg/L] in the 500% antithrombin group and 34 microg/L [95% CI, 20-48 microg/L] in the placebo group at 4 hours), and D-dimer (0.2 microg/L [95% CI, 0.1-0.2 microg/L] in the 500% antithrombin group and 0.5 microg/L [95% CI, 0.4-0.7 microg/L] in the placebo group). Recombinant human antithrombin decreased peak interleukin-6 levels by 40% (222 pg/mL [95% CI, 148-295 pg/mL] and 216 pg/mL [95% CI, 112-320 pg/mL] in the 500% and 200% antithrombin groups, respectively, versus 357 pg/mL [95% CI, 241-474 pg/mL] in the placebo group; P < .001 by ANOVA). Finally, infusion of recombinant human antithrombin rapidly and transiently decreased neutrophil counts (by 19% [95% CI, 8%-30%] in the 500% antithrombin group versus 6% [95% CI, 1%-10%] in the placebo group, P = .002 by Kruskal-Wallis ANOVA) and monocyte counts (by 30% [95% CI, 16%-44%] in the 500% antithrombin group and 18% [95% CI, 9%-28%] in the 200% antithrombin group versus 8% [95% CI, 5%-20%] in the placebo group, P = .04) before LPS challenge, indicating that recombinant human antithrombin directly interacts with these leukocyte subsets. In summary, recombinant human antithrombin dose-dependently inhibited tissue factor-triggered coagulation. Effects on leukocytes and inhibition of interleukin-6 release seem to represent specific pharmacodynamic properties of recombinant human antithrombin.
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PMID:Recombinant human antithrombin inhibits thrombin formation and interleukin 6 release in human endotoxemia. 1641 39

A 7-year-old female suddenly exhibited high fever and convulsions, and entered a semi-coma. She also had thrombocytopenia, elevated aminotransferase, prolonged prothrombin time and activated partial thromboplastin time, and hemophagocytes in the bone marrow. The brain magnetic resonance imaging revealed multiple low-intensity areas on the T1-weighted images, and high-intensity areas on the T2-weighted images bilaterally in the thalamus, the dorsal part of the pons, and the cerebellar white matter. The patient was diagnosed as having both acute necrotizing encephalopathy and hemophagocytic syndrome. Serum and cerebrospinal fluid interleukin-6 and tumor necrosis factor-alpha were elevated to the same high levels (serum:cerebrospinal fluid interleukin-6, 103:101 pg/mL; tumor necrosis factor-alpha 753:753 pg/mL). The clinical symptoms and the magnetic resonance imaging findings improved immediately after the administration of dexamethasone. These results suggest that the hypercytokinemia and the hyperpermeability of both the blood-brain barrier and the capillary walls of the central nervous system might be essential in the pathogenesis of acute necrotizing encephalopathy, and that early steroid therapy might be effective in these conditions.
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PMID:Acute necrotizing encephalopathy associated with hemophagocytic syndrome. 1663 10

Drug-eluting stents (DESs) deliver biphasic (early and late) elution of anti-inflammatory compounds. We therefore hypothesized that DESs would be associated with early reductions in inflammatory biomarker release after percutaneous coronary intervention (PCI). A total of 741 patients with non-ST-elevation acute coronary syndrome underwent PCI in the Randomized Trial to Evaluate the Relative PROTECTion against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia among Anti-Platelet and Anti-Thrombotic Agents (PROTECT) Thrombolysis In Myocardial Infarction 30 study of eptifibatide and reduced-dose antithrombin compared with bivalirudin. Serial biomarkers C-reactive protein, troponin, creatine kinase-MB, soluble CD40 ligand, interleukin-6, prothrombin fragment F1.2, and RANTES (regulated on activation, normal T-cell expressed and secreted) were assessed through 24 hours after PCI. DES use was at the investigator's discretion. Patients treated with DESs (n = 665) versus bare metal stents (n = 139) were more likely to have patent arteries before PCI (92.0% vs 86.6%, p = 0.04), Thrombolysis In Myocardial Infarction myocardial perfusion grade 3 (57.9% vs 47.7%, p = 0.033), and the left anterior descending artery as the culprit artery (38.5% vs 18.3%, p <0.001). The increase in C-reactive protein and troponin was lower among patients undergoing DES implantation (median 2.1 vs 3.5 mg/L for C-reactive protein, median 0.11 vs 0.41 ng/ml for troponin), even after adjustment for randomized treatment, clopidogrel before treatment, diabetes mellitus status, epicardial patency, left anterior descending artery location, and myocardial perfusion (p = 0.036 and p = 0.039, respectively). Interleukin-6 was lower with DESs on univariate analysis but not multivariate analysis. Creatine kinase-MB, soluble sCD40 ligand, prothrombin fragment F1.2, and RANTES did not differ by DES use. In conclusion, patients undergoing DES implantation achieved more reductions in periprocedural markers of inflammation and necrosis than patients receiving bare metal stents among those with non-ST-elevation acute coronary syndrome.
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PMID:Comparison of effects of bare metal versus drug-eluting stent implantation on biomarker levels following percutaneous coronary intervention for non-ST-elevation acute coronary syndrome. 1705 55

Interleukin-6 (IL-6) is an important cytokine in liver regeneration, and elevated levels of IL-6 have been demonstrated in patients with chronic liver diseases (CLD). Many biological effects of IL-6 depend on naturally occurring soluble IL-6 receptors. In the present study we measured the concentrations of IL-6 and its soluble receptors in the sera of patients with CLD related to hepatitis C virus (HCV) infection. We studied 77 patients with varying degrees of HCV-related CLD. Serum levels of IL-6 and its soluble receptors (sIL-6R, sgp130) were measured by enzyme-linked immunosorbent assay. Serum IL-6 and sIL-6R were elevated in patients with CLD compared with healthy subjects. Serum levels of sgp130 did not differ between patients with chronic hepatitis and healthy subjects. However, in patients with liver cirrhosis, sgp130 was significantly elevated and was positively correlated with total bilirubin and negatively correlated with cholinesterase and prothrombin time. Our study demonstrated that in patients with HCV-related CLD, serum IL-6 and its soluble receptor levels are correlated with both liver function impairment and the degree of liver fibrosis. These observations suggest that the balance of IL-6 and its soluble receptors may correspond to the state of liver damage in patients with CLD.
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PMID:Serum levels of interleukin-6 and its soluble receptors in patients with hepatitis C virus infection. 1669 22

Although coagulopathy is known to be the major contributor to a poor outcome of traumatic brain injury (TBI), the mechanisms that trigger coagulation abnormalities have not been studied in detail. We undertook a prospective observational study at a neurosurgical ICU (NICU) in a university hospital. We examined 11 patients with severe isolated TBI, at admittance to the hospital and during the next 3 days. We collected cerebrovenous blood samples from a jugular bulb catheter, arterial blood, and cerebrospinal fluid (CSF) samples. We measured concentrations of thrombin-antithrombin complex (TAT), fibrin D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), interleukin-6 (IL-6), and complement complex (C5b-9). All patients had some degree of consumption coagulopathy at the study start and a tendency to thrombocytopenia during the next few days. Levels of DD (3.6 +/- 2.7 mg/L), TAT (86 +/- 72 microg/L) and F1 + 2 (5.9 +/- 6.8 nmol/L) were significantly increased shortly after the trauma compared to reference values, with considerable transcranial gradients for TAT (49 microg/L) and F1 + 2 (3.2 nmol/L). Compared to controls, IL-6 levels were increased more than a hundredfold in both blood (283 +/- 192 ng/L) and CSF (424 +/- 355 ng/L) samples, with a transcranial gradient at the study start (107 ng/L). C5b-9 levels were moderately increased in blood samples, 270 +/- 114 microg/L, versus controls, 184 +/- 39 (p < 0.05). We conclude that activation of the coagulation system takes place during the passage of blood through the damaged brain, and is already evident hours after the trauma. IL-6 and activation of the complement system (C5b-9) co-vary with hemostatic parameters in TBI patients.
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PMID:Coagulation abnormalities associated with severe isolated traumatic brain injury: cerebral arterio-venous differences in coagulation and inflammatory markers. 1726 81

Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-induced acute systemic inflammation. The study is a randomized (3:2 active:placebo), double-blind, placebo-controlled parallel group trial. Twenty healthy male volunteers randomly received either reparixin (12) or placebo (8) intravenously. One hour after the start of reparixin/placebo infusion a bolus of 2 ng/kg endotoxin was infused over 1-2 min. Blood samples were obtained over 24 h. Reparixin, being metabolized to ibuprofen, suppressed serum thromboxane B2 levels by 78 percent compared to baseline and control at 8 h. LPS-induced neutrophilia was not significantly affected by reparixin in human volunteers. Consistently, reparixin did not alter the lymphocyte or monocyte counts and had no effect on LPS-induced systemic inflammation as measured by tumor necrosis factor alpha (TNF-alpha) or interleukin-6 (IL-6) release. Regulation of IL-8 receptors CXCR1 and 2 and the degranulation marker CD11b showed the expected kinetics. Reparixin had no effect on thrombin formation as measured by prothrombin fragment (F1+2). In conclusion, our study showed that reparixin was safe but had no impact on endotoxin induced inflammation. In contrast to previous studies with its metabolite ibuprofen, reparixin does not enhance inflammation in this model.
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PMID:Reparixin, a specific interleukin-8 inhibitor, has no effects on inflammation during endotoxemia. 1734 25


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