The role of complement in meconium aspiration syndrome.

The complement system is part of the host defense with a number of biological effects, most of which contribute to the inflammatory reaction by activation of cells like leukocytes and endothelial cells. An intact complement system is required for protection against infection and for maintaining internal inflammatory homeostasis. However, the system is a double-edged sword as improperly or uncontrolled activation is disadvantageous and potentially harmful for the host. Meconium aspiration syndrome (MAS) is associated with a local inflammatory reaction in the lungs, frequently described as a chemical pneumonitis. Cytokines, arachidonic acid metabolites and reactive oxygen species are involved in this reaction. We have recently documented that meconium is a potent activator of complement in vitro and in an experimental piglet model of MAS, the latter presenting with an inflammatory profile closely resembling systemic inflammatory response syndrome. We postulate that complement activation may contribute to the pathogenesis of MAS.

Meconium aspiration syndrome induces complement-associated systemic inflammatory response in newborn piglets.

The pathophysiology of meconium aspiration syndrome (MAS) is complex. We recently showed that meconium is a potent activator of complement. In the present study, we investigated whether the complement activation occurring in experimental MAS is associated with a systemic inflammatory response as judged by granulocyte activation and cytokine and chemokine release. MAS was induced by the instillation of meconium into the lungs of newborn piglets (n = 8). Control animals (n = 5) received saline under otherwise identical conditions. Haemodynamic and lung dynamic data were recorded. Complement activation, revealed by the terminal sC5b-9 complex (TCC), and cytokines [interleukin (IL)-6 and IL-8] were measured in plasma samples by enzyme immunoassays. The expression of CD18, CD11b and oxidative burst in granulocytes was measured in whole blood by flow cytometry. Plasma TCC increased rapidly in the MAS animals in contrast with controls (P < 0.0005). The TCC concentration correlated closely with oxygenation index (r = 0.48, P < 0.0005) and ventilation index (r = 0.57, P < 0.0005) and inversely with lung compliance (r = -0.63, P < 0.0005). IL-6 and IL-8 increased in MAS animals compared with the controls (P = 0.002 and P < 0.001, respectively). Granulocyte oxidative burst declined significantly in the MAS animals compared with the controls (P < 0.02). TCC correlated significantly with IL-6 (r = 0.64, P < 0.0005) and IL-8 (r = 0.32; P = 0.03) and inversely with oxidative burst (r = -0.37; P = 0.02). A systemic inflammatory response associated with complement activation is seen in experimental MAS. This reaction may contribute to the pathogenesis of MAS.