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-alpha 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.
Lindenskov
Paal H H
PH
Department of Pediatric Research (PFI), Rikshospitalet University Hospital, N-0027 Oslo, Norway. p.h.h.lindenskov@klinmed.uio.no
Castellheim
Albert
A
Aamodt
Geir
G
Saugstad
Ola D
OD
Mollnes
Tom E
TE
D000818:Animals; D000831:Animals, Newborn; D003167:Complement Activation / Q000276:immunology*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000503:physiopathology; D008471:Meconium Aspiration Syndrome / Q000276:immunology* / Q000401:mortality* / Q000503:physiopathology; D034421:Sus scrofa; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007375:Interleukin-1; C047610:SC5b-9 protein complex; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins