Selective modulation of monocyte and neutrophil responses with activated protein C in preterm infants

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 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.

Automated summary

This study aimed to investigate the response of neutrophils and monocytes in preterm infants to lipopolysaccharide (LPS) and activated protein C (APC) stimulation. Results showed that APC significantly reduced LPS-induced reactive oxygen intermediate (ROI) release from neutrophils. Monocyte ROI production in preterm infants was higher compared to adults and term controls. Neutrophil toll-like receptor 4 (TLR4) baseline expression was higher in term controls compared to preterm infants. Therefore, APC may reduce tissue damage in preterm infants by decreasing ROI release.