Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23).
A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.
von der Möhlen
M A
MA
Center of Thrombosis, Hemostasis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands.
van Deventer
S J
SJ
Levi
M
M
van den Ende
B
B
Wedel
N I
NI
Nelson
B J
BJ
Friedmann
N
N
ten Cate
J W
JW
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004731:Endotoxins / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007447:Invertebrate Hormones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
D000925:Anticoagulants; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D004731:Endotoxins; D007447:Invertebrate Hormones; D008565:Membrane Proteins; D011994:Recombinant Proteins; C034705:antilipopolysaccharide factor (Limulus); C025357:endotoxin binding proteins