COMPLEMENT ACTIVATION IN RELATION TO CAPILLARY LEAKAGE IN CHILDREN WITH SEPTIC SHOCK AND PURPURA

assess the relationship between capillary leakage and inflammatory med iators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later; from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Pa rameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phosp holipase A,, and C-reactive protein [CRP]), to neutrophil degranulatio n (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4 b/c, and C3- and CI-CRP complexes), and to complement regulation (func tional and inactivated C1 inhibitor and C4BP) were determined. The deg ree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortal ity (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin legions, were sig nificantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1. 9 times higher in survivors). Mortality was independently related to t he levels of C3b/c and C3-CRP complexes. In agreement with this, level s of complement activation products correlated well with the PRISM sco re or capillary leakage. Thus, these data show that complement activat ion in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.