[Skip to Content]
[Skip to Content Landing]
Article
July 1995

Interleukin-1 Blockade Attenuates Mediator Release and Dysregulation of the Hemostatic Mechanism During Human Sepsis

Author Affiliations

From the Departments of Surgery (Drs Boermeester and van Leeuwen) and Internal Medicine (Dr Hack), Free University Hospital, Amsterdam; Central Laboratory of the Netherlands, Red Cross Blood Transfusion Services (Drs Wolbink and Hack); and the Laboratory for Experimental and Clinical Immunology, the University of Amsterdam (Drs Wolbink and Hack); and the Laboratory of Surgical Metabolism, Department of Surgery, Cornell University Medical College, New York, NY (Ms Coyle and Dr Lowry).

Arch Surg. 1995;130(7):739-748. doi:10.1001/archsurg.1995.01430070061012
Abstract

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-α2-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–α1-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.(Arch Surg. 1995;130:739-748)

×