Both studies suggest that the VEGF is produced intrathecally and may contribute to the blood-brain barrier disruption. Our data would also be consistent with intrathecal production of growth factors. We demonstrated higher CSF than plasma concentrations in paired samples, and higher concentrations of VEGF and FGF in the CSF of children who selleck died. We previously reported data that suggest a compartmentalized host response in pneumococcal meningitis [33]. In contrast to the study by van der Flier [48], we found no association between the CSF growth factors and the CSF white cell count.Neutrophils have been shown to secrete VEGF in response to pneumococcal stimulation, and we suggest that VEGF may play a role as a mediator of vascular permeability [50].
VEGF and PDGF are working in a complex relation with Ang-1 and Ang-2 to promote endothelial cell survival and to prevent apoptosis [17]. Our data showing a favorable outcome in children with higher plasma levels of FGF, VEGF, PDGF, and Ang-1 would be consistent with this theory. Ang-2 appears to be acting as an antagonist to the other angiogenic factors and correlates positively with disease severity. The dysregulation of Ang-1 and Ang-2 in severe sepsis may contribute to the endothelial dysfunction and increased vascular permeability that lead to multiorgan failure and mortality.ConclusionsWe have shown that low plasma VEGF, PDGF, FGF, and Ang-1 concentrations are associated with an unfavorable outcome in children with severe bacterial infection, the association being independent of confounding factors in the case of Ang-1.
High Ang-2 concentrations are associated with mortality. In bacterial meningitis, our data support the concept of intracerebral production of growth factors, with increased CSF concentrations in nonsurvivors. VEGF, PDGF, FGF, Ang-1, and Ang-2 may be key players in the endothelial dysregulation seen in severe bacterial infection, or they may simply reflect an attempt by the host to repair endothelial damage. The measurement of these five factors might be useful (a) as prognostic markers of outcome, and (b) in identifying children who might benefit from adjunctive new therapies. Further studies are needed to identify the exact mechanism by which the angiopoietins might affect endothelial function in severe bacterial infection.Key messages? Mean VEGF, PDGF, and FGF concentrations are higher in survivors than in nonsurvivors.
? Mean Ang-1 is significantly increased, and Ang-2 significantly decreased, in survivors compared Entinostat with nonsurvivors.? Low Ang-1 is independently associated with mortality.? In bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF VEGF and FGF concentrations were higher in nonsurvivors than in survivors.? Ang-1 could be a useful prognostic marker.