Related Experiment Video
Updated: Aug 22, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Complement activation reflects severity of meconium aspiration syndrome in newborn pigs
Paal H H Lindenskov1, Albert Castellheim, Geir Aamodt
1Department of Pediatric Research (PFI), Rikshospitalet University Hospital, N-0027 Oslo, Norway. p.h.h.lindenskov@klinmed.uio.no
Abstract:
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.
Insights
Complement activation, indicated by the terminal sC5b-9 complex (TCC), plays a key role in meconium aspiration syndrome (MAS) lung injury and inflammation in newborns. This complement pathway activation precedes cytokine release, suggesting a primary role in MAS pathophysiology.
Area of Science:
- Neonatal Medicine
- Immunology
- Pulmonary Medicine
Background:
- Meconium aspiration syndrome (MAS) is a severe neonatal condition with an unclear inflammatory basis.
- The role of the complement system in MAS-related lung injury and systemic inflammation requires further investigation.
Purpose of the Study:
- To explore the involvement of complement activation in the pulmonary and systemic inflammatory responses during experimental MAS.
- To investigate the relationship between complement activation, lung dysfunction, and cytokine release in MAS.
Main Methods:
- Meconium aspiration syndrome (MAS) was induced in 12 piglets via lung instillation; 6 controls received saline.
- Hemodynamics, lung function, plasma complement activation (sC5b-9 complex/TCC), and cytokine levels (IL-1beta, TNF-alpha, IL-10) were measured over 5 hours.
- Correlations between TCC, lung dysfunction indices (oxygenation, ventilation, compliance), and cytokine levels were analyzed.
Main Results:
- Terminal complement complex (TCC) levels significantly increased in MAS piglets compared to controls (p <0.0005).
- Elevated TCC correlated strongly with impaired oxygenation (r=0.51) and ventilation (r=0.64), and inversely with lung compliance (r=-0.22).
- Pro-inflammatory cytokines IL-1beta and TNF-alpha increased significantly in MAS, with complement activation preceding their release. Higher TCC was observed in non-surviving MAS piglets.
Conclusions:
- Complement activation, measured by TCC, is significantly elevated in experimental MAS and closely linked to lung dysfunction.
- Complement activation appears to precede the release of inflammatory cytokines, suggesting a primary role in MAS pathophysiology.
- These findings highlight complement as a potential therapeutic target for mitigating lung injury in MAS.
