Complement activation reflects severity of meconium aspiration syndrome in newborn pigs

Meconium aspiration syndrome (MAS) is a serious condition in newborns, associated with a poorly characterized inflammatory reaction. The aim of this study was to investigate a possible role for complement in pulmonary pathophysiology and systemic inflammation in experimental MAS. MAS was induced by instillation of meconium into the lungs of 12 hypoxic piglets. Six controls received saline under otherwise identical conditions. Hemo- and lung dynamics were recorded for 5 h. Plasma complement activation, revealed by the terminal sC5b-9 complex (TCC), and cytokines were measured by enzyme immunoassays. TCC increased substantially in MAS animals compared with controls (p < 0.0005). The increase in TCC correlated with lung dysfunction: closely with oxygenation index (r = 0.51, p < 0.0001) and ventilation index (r = 0.64, p < 0.0001) and inversely with lung compliance (r = -0.22, p = 0.05). IL-1beta and tumor necrosis factor-a increased significantly in MAS animals compared with the controls (p = 0.004 and 0.008, respectively). The cytokine increase occurred later than TCC and showed correlations with lung dysfunction similar to TCC. IL-10 did not discriminate between MAS animals and controls (p = 0.32). Finally, the subgroup of MAS animals that died (n = 5) had substantially higher TCC concentration compared with the surviving MAS animals (n = 7; p < 0.0005). TCC increased substantially in MAS and was closely correlated to lung dysfunction. Complement activation preceded cytokine release, which may suggest a primary role for complement in the pathophysiology of MAS.