VASCULAR ENDOTHELIAL GROWTH FACTOR IS INCREASED DURING THE FIRST 48 HOURS OF HUMAN SEPTIC SHOCK AND CORRELATES WITH VASCULAR PERMEABILITY

Abstract

Meningococcal septic shock is an important cause of morbidity and mortality in children and young adults worldwide and is the prototypical gram-negative septic shock. One of the key factors in the development of shock is increased microvascular permeability. Vascular endothelial growth factor (VEGF) is a central factor in angiogenesis and is an important mediator of vascular permeability. Thirteen patients with meningococcal infection (eight presenting with shock) were investigated in the early phase of invasive meningococcal disease. Cytokines, complement activation, and VEGF plasma concentrations were measured during the first 48 h on the pediatric intensive care unit. Increased cytokine concentrations and activation of the complement system were observed. VEGF plasma concentrations were increased (median 193 pg/mL, range 71-1082) and were highest in the presence of shock (208 pg/mL, 169-1082) compared with patients presenting without shock (92 pg/mL range 71-299). VEGF concentration at admission correlated with the severity of disease (pediatric risk of mortality score, R=0.90 [Spearman], P=0.0001) and the amount of fluids administered within the first 24 h (R=0.90, P<0.0001). In all patients, a decrease in VEGF was associated with a decrease in fluid intake during t=24 to 48 h. The results suggest that apart from correlation with IL-1 beta, -10, -12, and complement activation, microvascular permeability in sepsis is also closely linked to the plasma concentration of VEGF. The role of VEGF in sepsis-associated increased microvascular permeability needs further exploration and may represent a new therapeutic target.