title: 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.
authors.affiliation: Department of Intensive Care Medicine, University Medical Centre, St. Radboud, 6500 HB Nijmegen, The Netherlands. p.pickkers@ic.umcn.nl
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Lucas van
authors.initials: Lv
authors.lastname: Eijk
authors.forename: Hans van der
authors.initials: Hv
authors.lastname: Hoeven
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Marcel van
authors.initials: Mv
authors.lastname: Deuren
mesh_terms: D002199:Capillary Permeability; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000097:blood* / Q000150:complications / Q000401:mortality; D012772:Shock, Septic / Q000097:blood* / Q000209:etiology; D013997:Time Factors; D042442:Vascular Endothelial Growth Factors / Q000097:blood*
chemical_list: D016207:Cytokines; D042442:Vascular Endothelial Growth Factors