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)

To assess the effect of interleukin-6 (IL-6) on the coagulation and the fibrinolytic systems, we administered a single subcutaneous injection of recombinant glycosylated human interleukin-6 (r-hIL-6) 100 micrograms per kg body weight) to four baboons (Papio ursinus). Four saline injected baboons served as controls. In serial plasma or serum samples collected over a period of seven days we measured several key parameters of the coagulation and the fibrinolytic systems, IL-6 and a set of acute phase proteins. Three hours after the injection, the serum IL-6 levels peaked at 50 ng/ml and then gradually declined with a terminal half-life of around 4 hours. The biological efficacy was demonstrated by the significant increases of several acute phase proteins, circulating platelets and the decrease of prealbumin and fibronectin. Between days 1 and 3, marked effects on the coagulation system were observed with a prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time. Plasma concentrations of fibrinopeptide A and D-dimer increased. The antithrombin III antigen and activity levels decreased, but the thrombin-antithrombin III complex concentrations did not change. The fibrinolytic system rapidly showed striking modifications after 6-8 hours, the concentrations of tissue-type plasminogen activator and of plasminogen activator inhibitor type 1 peaked at respectively four and thirty times the basal concentrations. No changes were seen in the control group. We conclude that besides its well-known acute phase inducing and hematopoietic activities, subcutaneous rhIL-6 also modulates several parameters of the coagulation and the fibrinolytic systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons. 794 65

Tumor necrosis factor (TNF) is considered to be a pivotal mediator of endotoxin-induced lethality. To assess the intermediate role of TNF in specific systemic inflammatory responses known to contribute to tissue injury in endotoxemia, eight healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In four of these animals the administration of endotoxin was followed immediately by a bolus intravenous injection of an anti-TNF monoclonal antibody (15 mg/kg). Treatment with anti-TNF completely prevented the endotoxin-induced increase in serum TNF activity, and profoundly reduced the appearance of interleukin-6 and -8 (both P < .05). Neutrophilia and lymphopenia were not affected by anti-TNF, whereas neutrophil degranulation, as measured by the plasma concentrations of elastase-alpha 1-antitrypsin complexes, was only slightly reduced (peak levels after endotoxin alone 31.0 +/- 3.4 ng/mL, versus 25.5 +/- 3.4 ng/mL after endotoxin with anti-TNF; P < .05). Anti-TNF did not influence endotoxin-induced activation of the coagulation system, as reflected by unchanged increases in the plasma concentrations of the prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes. In contrast, anti-TNF strongly attenuated the activation of the fibrinolytic system, ie, peak plasma levels of plasmin-alpha 2-antiplasmin were 33.8 +/- 11.1 nmol/L after endotoxin alone and 17.0 +/- 2.9 nmol/L after endotoxin with anti-TNF (P < .05). These results suggest that TNF is not the common mediator of systemic inflammatory changes in low-grade endotoxemia. Moreover, the finding that in this mild model anti-TNF specifically inhibited fibrinolysis suggests that treatment with anti-TNF potentially may enhance the tendency towards microvascular thrombosis in sepsis.
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PMID:Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. 828 42

To study the mechanism underlying the high lipoprotein (a) [Lp(a)] level in uremic patients on chronic hemodialysis, we investigated the levels of Lp(a), acute phase reactants (C-reactive protein and sialic acid), and interleukin-6 (IL-6) in 54 dialysis patients. The mean [95% CI] Lp(a) level was increased in the hemodialysis patients compared with the 30 controls (30 [25-36] vs. 18 [14-23] mg/dl, p < 0.005). Among dialysis patients, 46% had an Lp(a) level > 30 mg/dl, which was significantly higher than the percentage in the control group (17%). The levels of C-reactive protein, sialic acid, and IL-6 were also increased in dialysis subjects compared with controls (200 [134-299] vs. 37 [24-58] micrograms/dl, p < 0.0001; 63 [59-66] vs. 54 [52-56] mg/dl, p < 0.002; and 9.2 [7.8-11] vs. 5.5 [5.0-6.1] pg/ml, p < 0.0005, respectively). The Lp(a) level was positively correlated with that of C-reactive protein (r = 0.415, p < 0.002), sialic acid (r = 0.426, p < 0.002), and IL-6 (r = 0.298, p < 0.05) in the hemodialysis patients, but not in the controls or non-dialysis uremic patients. The Lp(a) level in the dialysis patients was also positively correlated with activation markers of coagulation (thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex, p < 0.005). These results indicate that the Lp(a) level is closely related to the acute phase reaction and hypercoagulability in chronic hemodialysis patients.
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PMID:High lipoprotein (a) levels in chronic hemodialysis patients are closely related to the acute phase reaction. 856 Apr 4

The aim of this study was to characterize the changes in the quantitative expression of beta 2-integrins and L-selectin detected by means of fluorochrome-conjugated monoclonal antibodies and flow cytometry on leukocytes in the systemic circulation after a major musculoskeletal trauma, i.e. hip replacement surgery, and to relate these changes to parameters of the acute-phase response [plasma acute-phase reactants (C-reactive protein, CRP, and interleukin-6, IL-6) and parameters of coagulation activation (thrombin-antithrombin III complexes, TAT)]. Eight patients with either primary or secondary osteoarthritis of the hip received uncemented total hip prostheses. LFA-1 (CD11a/CD18) was upregulated on granulocytes during the operation. MAC-1 (CD11b/CD18) expression on monocytes increased to peak levels 20 h after surgery, whereas the L-selectin (CD62L) expression on monocytes and granulocytes reached peak values at the end of surgery. The changes in expression of LFA-1 on monocytes, MAC-1 on granulocytes and p150,95 (CD11c/CD18) on monocytes and granulocytes during and after the operation did not reach statistical significance. TAT and IL-6 increased during surgery and reached peak values at the end of the operation and 20 h after surgery, respectively. In contrast, CPR concentrations increased after surgery with peak levels 44 h postoperatively. Significant upregulation of LFA-1 on granulocytes and L-selectin on monocytes and granulocytes preceded the increase in IL-6 which again preceded the increase in CRP. However, the up- or downregulation of leukocyte beta 2-integrins and L-selectin during and after surgery was not significantly correlated with the increase in IL-6. The increases in TAT correlated well with the upregulation of L-selectin on monocytes, but not with the beta 2-integrins known to participate in the coagulation process in vitro. The rise in CRP was inversely correlated with the maximal increase in expression of MAC-1 on monocytes. In conclusion, the changes in leukocyte adhesion molecules during and after surgery indicate changes in critical leukocyte functions. The lack of correlation between quantitative up- and downregulation of leukocyte beta 2-integrins and parameters of the acute phase response suggests that these processes are regulated through independent pathways or that functional up- and downregulation of adhesion molecules, shedding, leukocyte-endothelial adhesion and mobilization of new unactivated cells may result in a net estimate of leukocyte activation not suspected to be positively correlated to acute-phase reactants.
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PMID:Expression of beta-2-integrins and L-selectin by leukocytes and changes in acute-phase reactants in total hip replacement surgery. 873 29

Twelve patients with acute pancreatitis admitted to our department between January 1993 and December 1994 were studied prospectively and classified into two groups (severe group, five patients; mild group, seven patients), according to the criteria for grading severity of acute pancreatitis proposed by the Research Committee for Intractable Diseases of the Pancreas, Japanese Ministry of Health and Welfare (1990). To evaluate markers for early estimation of the severity of acute pancreatitis, we measured serum changes in various parameters. In the severe group interleukin-6 (IL-6) levels were increased significantly 5, 24, 72, and 120 h after the onset (p < 0.01), compared with the mild group. C-reactive protein (CRP), thrombin antithrombin III, and alpha 2-plasmin inhibitor plasmin complex levels were significantly increased only at the 72-h time point. Peak values of interleukin-8 (IL-8) and soluble human E selectin were observed at 5 and 72 h, respectively, after the onset. There was a significant correlation between IL-6 at 5 h and both pancreatic secretory trypsin inhibitor (r = 0.85) and CRP (r = 0.94) at 72 h. We therefore conclude that IL-6 is a useful marker for assessment of the severity of acute pancreatitis in its early stages.
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PMID:Interleukin-6 is a useful marker for early prediction of the severity of acute pancreatitis. 959 21

The aim of the present study was to examine the changes of inflammatory and coagulation factors in blood of the internal jugular vein, not of peripheral vein, in patients with subarachnoid hemorrhage (SAH). The results show that while interleukin-6 (IL-6) and platelet activating factor (PAF) concentrations increased within first 4 days after SAH and remained elevated up to 14 days, interleukin-1 beta (IL-1 beta) showed a transient increase between 5-9 days after SAH and tumor necrosis factor-alpha (TNF-alpha) remained unchanged. Also different coagulation factors were increased between 5-9 days after SAH. Moreover, patients with delayed ischemic neurological deficits (DIND) displayed the highest levels of PAF and the coagulation factors, von Willebrand factor (vWF) and thrombin-antithrombin III complex (TAT). These results suggest that elevation of PAF and other inflammatory cytokines following SAH may cause the hypercoagulation state that is associated with cerebral vasospasm and internal jugular vein may be more adequate vessel for sampling blood to examine these factors.
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PMID:Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage. 934 29

Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities were greater in septic foals. Protein C antigen and antithrombin III activity were significantly lower in septic foals. Blood cultures were positive for growth and endotoxin was detected in 19 of 29 and 15 of 30 septic foals, respectively. In septicemic foals with detectable endotoxin in the plasma, the prothrombin and activated partial thromboplastin times were significantly longer and the plasminogen and antithrombin III activities were significantly less than in septic foals in which endotoxin was not detected. Twenty-three of the 34 septic foals did not survive. Septic foals that did not survive were most likely to have a positive blood culture in which a gram-negative organism was isolated. Histopathologic evidence of hemorrhage was evident in 11 foals at postmortem examination and thrombosis was identified in 2 foals. The prothrombin time was significantly longer in foals that had multisite hemorrhage at postmortem examination. The results of this study indicate that clinically relevant alternations in hemostatic and fibrinolytic indices occur in neonatal foals with septicemia and that derangements can be correlated with the presence of endotoxin in plasma. Derangements in hemostatic or fibrinolytic indices were helpful in identification of septic foals with increased risk of coagulopathy, but were not helpful in predicting hemorrhage as compared to thrombus formation. Survival of septicemic foals was correlated with gram-negative bacteremia, but not with the presence of endotoxin or coagulopathy.
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PMID:Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia. 950 57

Activation and inhibition of coagulation and fibrinolysis was analyzed in bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation and fibrinolysis was investigated in experiments in which the infusion of endotoxin was combined with the administration of monoclonal anti-TNF-alpha or anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in bronchoalveolar thrombin generation as measured by levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes. Markers for intrinsic pathway activation were not detectable, suggesting that the thrombin generation was mediated by the tissue factor-dependent route. Levels of antithrombin were low before the injection of endotoxin and not detectable hereafter. The administration of anti-IL-6 antibody completely abolished the endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was significantly depressed after endotoxin injection, mainly due to a striking increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin-induced effects on bronchoalveolar fibrinolysis could be blocked by the simultaneous administration of anti- TNF-alpha antibodies. We conclude that endotoxemia results in the activation of bronchoalveolar coagulation, which is apparently mediated by the tissue factor route of coagulation activation and which may be amplified by consumption of antithrombin III. Bronchoalveolar fibrinolytic activity is significantly abolished by increased levels of mainly PAI-2 after the injection of endotoxin. The endotoxin-induced effects on bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha seems to be the pivotal mediator of the endotoxin-induced depression of bronchoalveolar fibrinolysis.
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PMID:Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in endotoxemic chimpanzees. 965 12

Hemorrhage is known to induce the production of inflammatory cytokines such as interleukin-6 (IL-6). IL-6 plays an intermediate role as a factor in the activation of coagulation cascade and exerts a lethal effect in sepsis. To examine the effect of endogenous IL-6 on blood loss, we performed four experiments in female ddY mice. Enzyme immunoassay using an uncontrolled hemorrhage model, i.e., 75% tail resection, revealed the production of serum IL-6 (Experiment 1). We also measured cumulative blood loss and survival rate (Experiment 2); measured blood pressure and performed thrombelastogram (TEG) (Experiment 3); and measured plasma thrombin-antithrombin III (TAT) complex levels in two groups, one pretreated with 1 mg of anti-IL-6 monoclonal antibody (mAb), and one with normal rat globulin (NRG) using the same model (Experiment 4). The mAb group showed a significantly higher blood loss than the NRG group. All mice survived for 5 days in both groups. Blood pressure did not differ between either group. The TEG results suggest that administration of anti-IL-6 mAb caused mild suppression of coagulation activation, but did not affect fibrinolysis or platelets. In the mAb group, plasma TAT complex concentrations showed a significant decrease compared with the NRG group. In conclusion, hemorrhage-induced IL-6 may contribute to hemostasis through activation of coagulation, thus reducing blood loss.
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PMID:Bleeding induced interleukin-6 decreases blood loss via activation of coagulation. 1003 Jul 93

Sepsis is commonly associated with disturbances of the hemostatic balance. Most of the pathophysiological changes in sepsis are caused by endotoxin acting directly through endothelial injury or indirectly through release of cytokines with procoagulant effects. The relation between cytokines and hemostatic parameters was assessed in 32 patients with sepsis. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), tissue type plasminogen activator (t-PA) functional and antigen, plasminogen activator inhibitor-1 (PAI-1), plasminalpha2-antiplasmin complexes (PAP), D-Dimer, thrombomodulin (TM) and von Willebrand factor (vWF) were measured in patients and in 30 healthy subjects. The levels of cytokines TNF-alpha and interleukin-6 (IL-6) also were determined. A significant increase of F1+2, TAT, PAI-1, PAP, and D-Dimer was observed in septic patients as compared with controls (p<0.0001), whereas t-PA activity was significantly reduced (p<0.01). The markers of endothelial cell activation TM, vWF, and t-PA antigen also were elevated significantly as compared with the control group (p<0.01). Finally, we found a marked increase of TNF-alpha and IL-6 (p<0.0001). Whereas the increase of cytokine levels could be partially responsible for the hemostatic activation, it did not correlate with markers of endothelial activation in patients with sepsis.
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PMID:Endothelial cell and hemostatic activation in relation to cytokines in patients with sepsis. 1023 Aug 94


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