The Relationship between Plasminogen Activator Inhibitor-1 and Proinflammatory and Counterinflammatory Mediators in Children with Meningococcal Septic Shock

Abstract

Proinftammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6 and -8), counterinftammatory 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)-1 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-α, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-α 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-1 response to TNF-α may be associated with fatality, probably because of polymorphism of the PAI-1 gene.