Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia

• Published in: Blood Vol. 89; no. 8; pp. 2701 - 2705
• Main Authors: PAJKRT, D, VAN DER POLL, T, LEVI, M, CUTLER, D. L, AFFRIME, M. B, VAN DEN ENDE, A, TEN CATE, J. W, VAN DEVENTER, S. J. H
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15-04-1997
• Subjects: Adult; Biological and medical sciences; Blood Coagulation - drug effects; Blood Proteins - analysis; Blood. Blood coagulation. Reticuloendothelial system; Double-Blind Method; Endotoxemia - blood; Endotoxemia - chemically induced; Endotoxemia - therapy; Fibrinolysis - drug effects; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Interleukin-10 - pharmacology; Interleukin-10 - therapeutic use; Lipopolysaccharides - adverse effects; Male; Medical sciences; Pharmacology. Drug treatments; Premedication; Recombinant Fusion Proteins - pharmacology; Recombinant Fusion Proteins - therapeutic use; Human; Blood coagulation; Cytokine; Activation; Anticoagulant; Fibrinolysis; Randomization; Treatment; Interleukin 10; Double blind study; Models; Endotoxemia; Fibrinolytic
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v89.8.2701

Interleukin-10 (IL-10) has been found to inhibit lipopolysaccharide (LPS)-induced tissue factor expression by monocytes in vitro. To determine the effects of IL-10 on LPS-induced activation of the hemostatic mechanisms in vivo, we performed a placebo-controlled, cross-over study of human endotoxemia. Two groups of eight volunteers were challenged with LPS (4 ng/kg) on two occasions: once in conjunction with placebo, and once with recombinant human IL-10 (rhIL-10; 25 microg/kg). In group 1, placebo or rhIL-10 was given 2 minutes before LPS challenge, group 2 received placebo or rhIL-10 1 hour after LPS administration. Pretreatment with rhIL-10 reduced both LPS-induced activation of the fibrinolytic system (plasma concentrations of tissue type plasminogen activator, plasmin-alpha2-antiplasmin complexes, and D-dimer), and inhibition of fibrinolysis (plasma levels of plasminogen activator inhibitor 1), whereas posttreatment only inhibited the latter response. Both IL-10 pre- and posttreatment attenuated activation of the coagulation system (plasma levels of prothrombin fragment F1 + 2 and thrombin-antithrombin complexes). These results indicate that rhIL-10, besides its well-described inhibitory effects on cytokine release, potently modulates the fibrinolytic system and inhibits the coagulant responses during endotoxemia.