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Selective modulation of monocyte and neutrophil responses with activated protein C in preterm infants
Hassan O Eliwan1,2,3, William R G Watson1, Ashanty M Melo4
1UCD School of Medicine and Medical Science & Conway Institute for Biomolecular and Biomedical Science, University College, Dublin, Ireland.
Insights
Activated protein C (APC) reduced inflammatory responses in preterm infants. While APC lessened reactive oxygen intermediate (ROI) release, further research into APC variants is needed to mitigate hemorrhage risks.
Area of Science:
- Neonatal immunology
- Inflammatory response
- Preterm infant health
Background:
- Inflammation is linked to severe conditions in preterm infants, such as periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis.
- Activated protein C (APC) has demonstrated beneficial immunomodulatory effects.
Purpose of the Study:
- To investigate neutrophil and monocyte function in preterm infants (<32 weeks gestation) during the first week of life.
- To compare responses to lipopolysaccharide (LPS) and APC stimulation ex vivo with neonatal and adult controls.
Main Methods:
- Peripheral blood samples collected on days 1, 3, and 7 from preterm infants.
- Ex vivo stimulation with LPS, with and without APC.
- Flow cytometry analysis of toll-like receptor 4 (TLR4), CD11b expression, and reactive oxygen intermediate (ROI) release from neutrophils and monocytes.
Main Results:
- APC significantly reduced LPS-induced neutrophil ROI release in both adults and preterm infants.
- Preterm neonates exhibited increased baseline and LPS-induced monocyte ROI production compared to adult and term controls.
- Higher baseline neutrophil TLR4 expression was observed in term controls compared to preterm infants.
Conclusions:
- Elevated systemic ROI release in preterm infants may contribute to tissue damage; APC effectively reduced this release.
- The anticoagulant properties of APC necessitate further investigation into mutant forms with anti-inflammatory effects but reduced hemorrhage risk.
Background:
Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated protein c (APC) has shown positive immunomodulatory effects.
Objectives:
We aimed to study neutrophil and monocyte function in response to lipopolysaccharide (LPS) and APC stimulation ex vivo in preterm infants <32 weeks gestation over the first week of life compared to neonatal and adult controls.
Methods:
Peripheral blood was taken on day 1, 3, and 7 and stimulated with LPS in the absence or presence of APC. Expression of toll-like receptor 4 (TLR4) and CD11b and reactive oxygen intermediate (ROI) release from neutrophils and monocytes was examined by flow cytometry.
Results:
LPS induced neutrophil ROI in adults and preterm infants and was significantly reduced by APC. Baseline and LPS-induced monocyte ROI production in preterm neonates was increased compared to adult and term controls. Neutrophil TLR4 baseline expression was higher in term controls compared to preterm infants.
Conclusion:
Increased systemic ROI release in preterm infants may mediate tissue damage, ROI was reduced by APC. However, due to the high risk of hemorrhage further examination of APC mutant forms with anti-inflammatory but decreased anticoagulant properties is merited.
