Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perfluorotributylamine/Pluronic F68 Stem-Emulsion (FC43se), which is a blood substitute, was assessed for its effectiveness on disseminated intravascular coagulation (DIC) in the rat model. Rats were infused intravenously with 2.5 mg/kg of Escherichia coli lipopolysaccharide (Escherichia coli 055:B5 lipopolysaccharide B) for four hours. At the same time, FC43se or normal physiological saline was infused at 2.5 ml/kg/hr. The white blood cell and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), and the plasma levels of interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF alpha) were determined at 4 hr. The infusion of FC43se markedly prevented a decrease in platelet counts (p = 0.0004) and a prolongation of both PT and APTT (p < 0.05 and p < 0.03 each). The serum level of IL-1 beta and IL-4 showed no significant change. The serum level of IL-6, IL-10 and TNF alpha increased significantly (p = 0.0007, p = 0.0004 and p < 0.05 each) with infusion of FC43se in rats treated with bacterial endotoxin. FC43se has beneficial effects on endotoxin-induced DIC as an anticoagulant and anti-inflammatory cytokine induced agent.
 ...
PMID:Effect of FC43se on endotoxin-induced disseminated intravascular coagulation in rats. 1043 77

In order to determine whether prednisolone has a protective effect against the development of disseminated intravascular coagulation (DIC), we measured the effect of prednisolone on changes in hemostatic parameters and plasma levels of inflammatory cytokines in endotoxin-treated rats. Decreases in platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products and levels of thrombin-antithrombin III (TAT) complex following the administration of endotoxin, all of which are associated with DIC, were significantly suppressed by the administration of prednisolone. Heparin administration significantly suppressed changes in all these parameters except for the decrease in platelet count. The combination of prednisolone and heparin was more effective than either treatment alone. In order to determine whether these effects of prednisolone are correlated with the suppression of inflammatory cytokine production, we examined the relationship between changes in plasma levels of cytokine, the hemostatic parameters listed above, and mortality using a number of intervention regimens designed to alter events of the experimentally induced DIC. Changes in hemostatic parameters associated with DIC following 30 mg/kg per 4 h of endotoxin infusion were significantly suppressed by treatment with 1 mg/kg prednisolone 30 min before beginning endotoxin infusion, followed by administration of 250 U/kg heparin 2 h after the start of endotoxin infusion (prednisolone-endotoxin-heparin regimen). The heparin and prednisolone were administrated subcutaneously. The administration of prednisolone and heparin in the reverse order (i.e. heparin first and prednisolone second: heparin-endotoxin-prednisolone regimen) also suppressed changes in hemostatic parameters, albeit to a smaller degree. Cytokine production was also significantly suppressed by the first treatment, but was not affected by the regimen in which heparin was administered first. Administration of prednisolone alone or heparin alone 30 min before endotoxin significantly reduced the number of renal glomeruli with fibrin thrombi. Plasma levels of creatinine and alanine transferase were reduced only by prednisolone. Increased plasma levels of interleukin-1beta, tissue necrosis factor-alpha and interleukin-6 were suppressed by prednisolone but not by heparin, and there were significant correlations between plasma levels of TAT and cytokines. Prednisolone was more effective than heparin in reducing mortality at 24 h after 100 mg/kg over 4 h of endotoxin infusion (four of 20 versus 15 of 20 deaths for prednisolone and heparin, respectively). These findings suggest that prednisolone inhibits the development of endotoxin-induced DIC and reduces mortality by a different mechanism than heparin, possibly through suppressing the production of inflammatory cytokines. Prednisolone may be efficacious in preventing DIC and multiple organ dysfunction caused by endotoxin.
 ...
PMID:Prednisolone inhibits endotoxin-induced disseminated intravascular coagulation and improves mortality in rats: importance of inflammatory cytokine suppression. 1049 13

Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin's lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 x 10(9)/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 x 10(9)/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 x 10(9)/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 x 10(9)/L peripheral tumor cells (P = .0017). Due to massive side effects in the first patient treated with 375 mg/m(2) in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m(2) dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 x 375 mg/m(2) rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.
 ...
PMID:Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). 1049 91

We analyzed the changes in the serum levels of both interleukin-6 (IL-6), human hepatocyte growth factor (h-HGF), and type IV collagen 7S (7S) during the perioperative period of a hepatectomy and evaluated their relationship with systemic inflammatory response syndrome (SIRS). The study subjects consisted of 40 patients who underwent a hepatectomy. In 14 out of 40 patients, postoperative SIRS(+) was observed. Between the SIRS(+) and SIRS(-) cases, there were significant differences in the preoperative values of prothrombin time, hepaplastin test, cholinesterase, and indocyanine green retention at 15 min (P < 0.01). Compared with the SIRS(-) cases, the IL-6, h-HGF, and 7S of the SIRS(+) cases fluctuated in a higher range and remained significantly higher after postoperative day 1 (P < 0.05). Eight out of 14 SIRS(+) patients had postoperative complications. In the 8 SIRS(+) patients with postoperative complications and in the 4 patients in which the SIRS(+) state lasted 3 days or longer, the 7S levels were significantly higher during the perioperative period (P < 0.05). In the SIRS(+) cases, the postoperative levels of IL-6 and h-HGF, as well as pre- and postoperative levels of 7S, were elevated. We therefore consider these levels to be risk factors for complications during the perioperative period of a hepatectomy.
 ...
PMID:Significant changes in the serum levels of IL-6, h-HGF, and type IV collagen 7S during the perioperative period of a hepatectomy: relevance to SIRS. 1081 74

Platelets and leucocytes are important effector cells of the haemostatic and inflammatory responses to tissue injury. To investigate the effects of surgical trauma on platelet activation (assessed by measuring levels of P-selectin and beta-thromboglobulin), leucocyte activation (CD11b expression) and leucocyte-platelet interactions (leucocyte-platelet complexes), 30 patients undergoing primary hip arthroplasty were studied before and at the end of surgery, and on days 1 and 10 post-operatively, using a whole-blood flow cytometry assay. The inflammatory response was followed by measurement of the levels of C-reactive protein and interleukin-6 in plasma, and the activation of coagulation was monitored by determination of prothrombin fragment 1+2 levels. On day 1 post-operatively a significantly increased expression of CD11b on monocytes was noted, but no direct correlation was found between monocyte activation and interleukin-6 production or C-reactive protein at this time point. The percentage of monocyte-platelet and neutrophil-platelet complexes was markedly increased on day 10 post-operatively compared with pre-operative levels, and levels of these complexes were significantly positively correlated with beta-thromboglobulin levels. Activation of coagulation (prothrombin fragment 1+2) on day 10 post-operatively was positively correlated with the extent of surgical trauma (duration of surgery, amount of blood loss) and with the increase in platelet activation (beta-thromboglobulin). In conclusion, hip arthroplasty induces platelet and coagulation activation, and also an inflammatory response that is maintained for more than 10 days post-operatively. This indicates an interaction between the immune and the haemostatic systems in the post-operative phase after hip arthroplasty.
 ...
PMID:Increases in circulating levels of monocyte-platelet and neutrophil-platelet complexes following hip arthroplasty. 1186 68

Effects of a 4-week course of recombinant human erythropoietin (rHuEpo) therapy on four circulating endothelium-derived cardiovascular risk markers were studied in 20 patients receiving maintenance hemodialysis in relation to surrogates of chronic inflammation, liver function, and arterial blood pressure. Soluble intercellular adhesion molecule-1 (sICAM-1), antigens of plasminogen activator inhibitor-1 (PAI-1:Ag) and von Willebrand factor (vWF:Ag), and soluble thrombomodulin (sTM) were determined by immunoenzymatic assays. C-reactive protein; alpha1 acid-glycoprotein; alpha1-antitrypsin; immunoglobulin M, A, and G; interleukin-6; lipoprotein(a); fibrinogen; total protein; albumin; total cholesterol; hepatitis B and C markers; liver enzymes; prothrombin time; and phosphorus were measured by routine methods. The rHuEpo treatment resulted in a 25% increase in sICAM-1 (Wilcoxon's p = 0.001), a 50% increase in PAI-1:Ag (p = 0.004), a 15% increase in sTM (p = 0.002), and did not change vWF:Ag levels. The increase in sICAM-1 concentration directly correlated with that of PAI-1:Ag (Spearman's rho = 0.483, p = 0.031). The rHuEpo-induced increases in hemoglobin, platelets, and pre-dialysis diastolic blood pressure levels did not correlate with the increments in the endothelial markers studied. In conclusion, short-term rHuEpo therapy activates vascular endothelium in patients receiving maintenance hemodialysis. This specific effect may influence cardiovascular risk.
 ...
PMID:Effects of recombinant erythropoietin therapy on circulating endothelial markers in hemodialysis patients. 1465 47

We evaluated the effects of surgical invasion and vascular injury on hemostatic abnormalities in seventeen ASA I-II patients undergoing prolonged surgeries of eight hours or more consisting of tumor excision, radical neck dissection and free flap reconstruction in the maxillofacial region. As molecular markers of blood coagulation and surgical invasion, prothrombin fragment 1 + 2 (F 1 + 2), interleukin-6 (IL-6), tissue-type plasminogen activator (tPA), thrombomodulin (TM) and plasmin alpha 2-plasmin inhibitor complex (PIC) were measured during surgery and on the first and second postoperative days. The F 1 + 2 values increased significantly during surgery and decreased postoperatively, and reached the maximum at the end of surgery. Changes in IL-6 and tPA were similar to those of F 1 + 2, and there was a correlation in the levels of F 1 + 2 and IL-6 (r = 0.54), tPA (0.41) and PIC (0.30) at each measurement time. PIC and TM, however, did not show statistically significant changes intra- and postoperatively, nor was there any correlation between F 1 + 2 and TM values. From these results, we conclude that inflammatory mediators and endothelial stimulation activated by surgical invasion may influence hypercoagulability. Vascular injury, however, did not act as the main coagulation factor during prolonged maxillofacial surgery.
 ...
PMID:[Effects of vascular injuries on hemostatic abnormalities in prolonged surgeries of maxillofacial malignant cancer]. 1199 46

Thrombin generation is increased in men with advanced prostate cancer. Thrombin has the ability to interact with, and affect the biology of, a variety of cell types including prostate cancer cell lines. We therefore looked for correlations between thrombin generation and other markers of disease activity in spot urine samples obtained from men with advanced prostate cancer. Excretion of part of the prothrombin activation peptide F(1+2) (called here iF2), interleukin-6 (IL-6), the bone turnover marker deoxypyridinoline (DpD), and vascular endothelial growth factor (VEGF) were quantitated in spot urine samples collected from 37 men with hormone-refractory prostate cancer. Following log transformation of the data, significant correlations were found by univariate analysis between the excretion of a marker of thrombin generation (iF2) and IL-6, DpD and VEGF, as well as between IL-6 and DpD or VEGF excretion. No correlation was found between any marker and serum PSA level. After multivariate analysis, a significant correlation remained between thrombin generation and IL-6 excretion. Analysis of a second urine specimen obtained from 19 of the subjects 1 to 7 months after the first also revealed a significant correlation between thrombin generation and IL-6, DpD, and VEGF excretion. These data provide evidence of a correlation between thrombin generation/coagulation system activation and IL-6 generation in patients with cancer. They provide a rationale for studying the effects of inhibitors of thrombin generation upon the biology of prostate cancer.
 ...
PMID:Correlates of thrombin generation in patients with advanced prostate cancer. 1254 Sep 69

Activated platelets facilitate thrombin generation by providing a catalytic surface on which coagulation activation occurs. The glycoprotein (GP) IIb/IIIa receptor might play a major role in this process as shown by in vitro and animal experiments. However, it is controversial whether the GPIIb/IIIa receptor facilitates tissue factor-induced thrombin generation in humans as well. We therefore investigated whether two clinically used GPIIb/IIIa antagonists (tirofiban and eptifibatide) may blunt TF-induced coagulation in humans. Thirty male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide, tirofiban or placebo over 5 hours in a randomized, double-blind, placebo-controlled, double-dummy parallel-group trial. Markers of thrombin generation (prothrombin fragment 1+2, thrombin-antithrombin complexes), fibrinolysis (D-dimer, plasmin-antiplasmin complexes) as well as inflammatory markers (interleukin-6, tumor necrosis factor-alpha) were measured by enzyme linked immunoasssays, TF-mRNA expression was quantified by RT-PCR. Neither eptifibatide nor tirofiban influenced LPS-induced coagulation activation or fibrinolytic activity. Additionally, the increase of TNF-alpha and IL-6 was similar in all groups. In conclusion, GPIIb/IIIa blockade with eptifibatide or tirofiban did not influence TF-induced coagulation activation in human low grade endotoxemia.
 ...
PMID:Blockade of GPIIb/IIIa by eptifibatide and tirofiban does not alter tissue factor induced thrombin generation in human endotoxemia. 1465 36

Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.
 ...
PMID:Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction. 1505 Apr 82


<< Previous 1 2 3 4 5 6 7 Next >>