In contrast to plasma concentrations, mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors (1,178 versus 216 pg/ml; P = 0.02; and 939 versus 501 pg/ml; P = 0.001, www.selleckchem.com/products/INCB18424.html respectively).Plasma Ang-1 and Ang-2 in children with severe bacterial sepsisPlasma Ang-2 on admission was significantly increased in children with severe bacterial infection compared with healthy controls, but Ang-1 was not significantly different (Table (Table3).3). No significant differences in Ang-1 and Ang-2 concentrations were noted between children with meningitis and those with pneumonia, but Ang-2 was significantly elevated in HIV-infected children. The mean plasma Ang-1 concentrations were significantly lower in children with SBI compared with those with NBI, but Ang-2 was significantly higher after adjustment for confounding variables.

Ang-1 and Ang-2 plasma concentrations were not significantly different between gram-positive and gram-negative infections (Table (Table3).3). Mean plasma Ang-1 concentrations were significantly higher, and Ang-2, significantly lower in survivors compared with nonsurvivors (Table (Table3).3). The ratio of lnAng-2 (natural log Ang-2) to lnAng-1 was higher in nonsurvivors compared with survivors (P = 0.03). Plasma Ang-1 concentrations were not significantly different in children with invasive pneumococcal disease compared with children with SBI caused by pathogens other than S. pneumoniae (Table (Table3).3). Plasma Ang-2 correlated positively with the pro- and antiinflammatory cytokines, IL-1Ra, IL-6, IL-8, and IL-10 (Table (Table44).

Table 4Correlation between plasma angiogenic factors and pro- and antiinflammatory cytokinesLogistic regression models for predicting mortality and SBIThe plasma values of VEGF, PDGF, FGF, Ang-1, and Ang-2 were log transformed and included in a multivariate stepwise logistic regression model, including HIV status, sex, diagnosis (pneumonia or meningitis), and admission lactate, as variables in the equation. Female sex (OR, 3.95; 95% CI, 1.33 to 11.76), and Ang-1 (OR, 0.23; 95% CI, 0.08 to 0.69) were significantly associated with mortality. By using a similar model, meningitis (OR, 5.91; 95% CI, 1.47 to 23.77), admission lactate (OR, 3.20; 95% CI, 1.20 to 8.57), VEGF (OR, 5.63; 95% CI, 1.32 to 24.11), Ang-1 (OR, 0.19; 95% CI, 0.06 to 0.62), and Ang-2 (OR, 5.40; 95% CI, 1.79 to 16.

30) were significantly associated with SBI (Table (Table55).Table 5Multivariate logistic regression model to predict mortality and SBIDiscussionOur study examined both growth factors and angiogenic factors in 293 children and demonstrates that among Malawian children with severe bacterial infection, high plasma VEGF, PDGF, FGF, and Ang-1 concentrations are associated with a favorable outcome. Drug_discovery In contrast, high Ang-2 concentrations are associated with an unfavorable outcome.