THE RELATIONSHIP BETWEEN PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND PROINFLAMMATORY AND COUNTERINFLAMMATORY MEDIATORS IN CHILDREN WITH MENINGOCOCCAL SEPTIC SHOCK

Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and inter leukin [IL]-6 and -8), counterinflammatory compounds (IL-IO and solubl e TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parame ters were determined in 38 patients with meningococcal septic shock, E leven patients (29%) died. Serum levels of pro- and counterinflammator y compounds and plasma levels of plasminogen activator inhibitor (PAI) -1 were significantly higher in nonsurvivors. The interval between app earance of petechiae and blood sampling was shorter in nonsurvivors th an in survivors (3.6 +/- 2.3 vs. 6.1 +/- 3.3 h; P = .04). This interva l correlated strongly with the levels of TNF-alpha, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1, However, with the exception of PAI-1, di fferences between concentrations of these mediators disappeared after adjustment for the interval, PAI-1 levels correlated with TNF-alpha co ncentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher i n nonsurvivors at a similar TNF-alpha concentration. Thus, an increase d PAI-I response to TNF-alpha map be associated with fatality, probabl y because of polymorphism of the PAI-I gene.