Marked increase in vascular endothelial growth factor concentrations during Escherichia coli endotoxin-induced acute inflammation in humans.

ABSTRACT

BACKGROUND: Bacterial endotoxins can induce the synthesis and release of vascular endothelial growth factor (VEGF), which may alter vascular permeability and cause vascular leakage. MATERIALS AND 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.