Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia.
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.
Pajkrt
D
D
Laboratory of Experimental Internal Medicine and Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, University of Amsterdam, The Netherlands.
van der Poll
T
T
Levi
M
M
Cutler
D L
DL
Affrime
M B
MB
van den Ende
A
A
ten Cate
J W
JW
van Deventer
S J
SJ
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001798:Blood Proteins / Q000032:analysis; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000628:therapy*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D011292:Premedication; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use
D001798:Blood Proteins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10