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.
Castellheim
A
A
Department of Pediatric Research, Rikshospitalet University Hospital, Oslo, Norway. albert.castellheim@klinmed.uio.no
Lindenskov
P H H
PH
Pharo
A
A
Aamodt
G
G
Saugstad
O D
OD
Mollnes
T E
TE
D000818:Animals; D000831:Animals, Newborn; D003167:Complement Activation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000503:physiopathology; D008471:Meconium Aspiration Syndrome / Q000150:complications* / Q000276:immunology* / Q000503:physiopathology; D016897:Respiratory Burst; D034421:Sus scrofa; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology* / Q000276:immunology* / Q000503:physiopathology
D016207:Cytokines