OBJECTIVE: To define the influence of interleukin-1 activity on coagulation and fibrinolytic system activation and the release of proinflammatory mediators in the early human response to severe infection. STUDY DESIGN:All patients with severe sepsis syndrome who were enrolled from two surgical centers that were participating in a randomized, double-blind, placebo controlled, multicenter, multinational trial of recombinant human interleukin-1 receptor antagonist in the treatment of sepsis syndrome. POPULATION: Twenty-six patients with sepsis syndrome received an intravenous loading dose of recombinant human interleukin-1 receptor antagonist (100 mg) or placebo followed by a continuous 72-hour infusion of recombinant human interleukin-1 receptor antagonist (1.0 [n = 9] or 2.0 [n = 8] mg/kg per hour) or placebo (n = 9). OUTCOME MEASURE: Responses up to 72 hours after initiation of treatment. RESULTS:Plasma levels of the anaphylatoxin C3a and thrombin-antithrombin III complexes were reduced in the high-dose recombinant human interleukin-1 receptor antagonist treatment group after 72 hours (P < .05). Similarly, parameters of fibrinolysis, tissue-type plasminogen activator, and plasminogen activator inhibitor type 1 but not plasmin-alpha 2-antiplasmin complexes, were also significantly reduced (P < .05) after 72 hours of treatment with a high dose of recombinant human interleukin-1 receptor antagonist. Neutrophil elastase-alpha 1-antitrypsin complexes and phospholipase A2 levels were also significantly reduced in the high-dose recombinant human interleukin-1 receptor antagonist treatment group after 72 hours. CONCLUSIONS: The results confirm that activation of the coagulation and fibrinolytic systems and release of soluble inflammatory mediators are consistently observed in patients with severe sepsis syndrome. Interleukin-1 activity contributes to activation of these processes as documented by the reduction in surrogate activation markers during recombinant human interleukin-1 receptor antagonist treatment.
RCT Entities:
OBJECTIVE: To define the influence of interleukin-1 activity on coagulation and fibrinolytic system activation and the release of proinflammatory mediators in the early human response to severe infection. STUDY DESIGN: All patients with severe sepsis syndrome who were enrolled from two surgical centers that were participating in a randomized, double-blind, placebo controlled, multicenter, multinational trial of recombinant humaninterleukin-1 receptor antagonist in the treatment of sepsis syndrome. POPULATION: Twenty-six patients with sepsis syndrome received an intravenous loading dose of recombinant humaninterleukin-1 receptor antagonist (100 mg) or placebo followed by a continuous 72-hour infusion of recombinant humaninterleukin-1 receptor antagonist (1.0 [n = 9] or 2.0 [n = 8] mg/kg per hour) or placebo (n = 9). OUTCOME MEASURE: Responses up to 72 hours after initiation of treatment. RESULTS: Plasma levels of the anaphylatoxin C3a and thrombin-antithrombin III complexes were reduced in the high-dose recombinant humaninterleukin-1 receptor antagonist treatment group after 72 hours (P < .05). Similarly, parameters of fibrinolysis, tissue-type plasminogen activator, and plasminogen activator inhibitor type 1 but not plasmin-alpha 2-antiplasmin complexes, were also significantly reduced (P < .05) after 72 hours of treatment with a high dose of recombinant humaninterleukin-1 receptor antagonist. Neutrophil elastase-alpha 1-antitrypsin complexes and phospholipase A2 levels were also significantly reduced in the high-dose recombinant humaninterleukin-1 receptor antagonist treatment group after 72 hours. CONCLUSIONS: The results confirm that activation of the coagulation and fibrinolytic systems and release of soluble inflammatory mediators are consistently observed in patients with severe sepsis syndrome. Interleukin-1 activity contributes to activation of these processes as documented by the reduction in surrogate activation markers during recombinant humaninterleukin-1 receptor antagonist treatment.
Authors: A Familian; A E Voskuyl; G J van Mierlo; H A Heijst; J W R Twisk; B A C Dijkmans; C E Hack Journal: Ann Rheum Dis Date: 2005-07 Impact factor: 19.103
Authors: Nikolai Siemens; Sonja Oehmcke-Hecht; Jörn Hoßmann; Sebastian B Skorka; Roel H T Nijhuis; Corinne Ruppen; Steinar Skrede; Manfred Rohde; Daniel Schultz; Michael Lalk; Andreas Itzek; Dietmar H Pieper; Christiaan J van den Bout; Eric C J Claas; Ed J Kuijper; Robert Mauritz; Parham Sendi; Herman F Wunderink; Anna Norrby-Teglund Journal: J Innate Immun Date: 2019-11-19 Impact factor: 7.349