The Relationship between Plasminogen Activator Inhibitor-l and Proinflammatory and Counterinflammatory Mediators in Children

Proinftammatory cytokines (tumor necrosis factor [TNF]-a and interleukin [IL]-6 and-8), coun-terinftammatory compounds (IL-I0 and soluble TNF receptors p55 and p75 [sTNFR-55 and-75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinftammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-l were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 ± 2.4 vs. 6.1 ± 3.3 h; P =.04). This interval correlated strongly with the levels of TNF-a, IL-6,-8, and-10, sTNFR-55 and-75, and PAl-I. However, with the exception of PAI-l, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-l levels correlated with TNF-a concentrations (r =.75; P <.001) and were 1.9 (P =.01) times higher in nonsurvivors at a similar TNF-a concentration. Thus, an increased PAI-l response to TNF-a may be associated with fatality, probably because of polymorphism of the PAl-1 gene. Septic shock with purpura is a serious life-threatening dis-ease in otherwise healthy children and young adults. The syn-drome is most frequently due to Neisseria meningitidis