Marked increase in vascular endothelial growth factor concentrations during Escherichia coli endotoxin-induced acute inflammation in humans.
BACKGROUND
Bacterial endotoxins can induce the synthesis and release of vascular endothelial growth factor (VEGF), which may alter vascular permeability and cause vascular leakage.


METHODS
The effect of acute systemic inflammation on VEGF concentration was measured in healthy males after an intravenous bolus infusion of Escherichia coli endotoxin (lipopolysaccharide, LPS, 20 IU kg-1) in a double-blind, placebo-controlled parallel group study. LPS administration was followed by an infusion of lepirudin (bolus 0.1 mg kg-1, continuous infusion of 0.1 mg kg-1 h-1, n = 12) or saline (n = 12).


RESULTS
Plasma VEGF increased from a mean of 15.1 pg mL-1 to 74.6 pg mL-1 5 h after LPS (P < 0.003). Body temperature, pulse rate, leukcytes, prothrombin fragment 1 + 2 (F1 + 2) and lactoferrin increased and platelets decreased after LPS (P < 0.05). The LPS-induced increase in VEGF was paralleled by the neutrophil cell degranulation marker lactoferrin but not by F1 + 2, and was not affected by lepirudin, which blunted F1 + 2 formation (P < 0.05).


CONCLUSIONS
Inflammation-induced activation of leukcytes rather than platelets plays a role in the marked increase in VEGF, which cannot be abrogated by antithrombotic therapy.
Mittermayer
F
F
Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
Pleiner
J
J
Schaller
G
G
Weltermann
A
A
Kapiotis
S
S
Jilma
B
B
Wolzt
M
M
D000208:Acute Disease; D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D016228:Endothelial Growth Factors / Q000097:blood*; D004731:Endotoxins; D004926:Escherichia coli; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008222:Lymphokines / Q000097:blood*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000925:Anticoagulants; D016228:Endothelial Growth Factors; D004731:Endotoxins; D006629:Hirudins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C083544:lepirudin