747 - Tiny Babies: Altered Innate Immunity during Sepsis

Publication Number: 2728.747

Dearbhla Byrne, Trinity College Dublin/RCPI, Dublin, Dublin, Ireland; Johana Isaza-Correa, Trinity College Dublin, Dublin, Dublin, Ireland; Aoife Branagan, McGill University Faculty of Medicine and Health Sciences, Montreal, PQ, Canada; Eleanor J. Molloy, Trinity College Dublin, Dublin, Dublin, Ireland

Background: Preterm infants are particularly susceptible to invasive bacterial infections. Despite advances in neonatal intensive care, mortality due to sepsis remains high in this population, particularly in those less than 25 weeks gestation. Dysregulated immune responses in preterm infants have been linked with multi-organ dysfunction and poor neurodevelopment outcomes.

Objective: Our aim was to evaluate the tiny babie’s innate immune response to sepsis at various gestations compared to their term counterparts.

Design/Methods: Preterm infants (less than 32 weeks gestation and/or less than 1500g) and neonatal controls were recruited prospectively. Blood samples were collected at baseline and during episodes of sepsis. Serial blood samples were collected on preterm infants. Whole blood was stimulated with or without lipopolysaccharide (LPS) in vitro. Flow cytometry was used to assess innate immune cell function on whole blood samples. Toll-like receptor (TLR)-4 (receptor for endotoxin/LPS) and CD11b expression (cell activation marker) were used as markers of activity for neutrophils (CD66b+), monocytes (CD14/CD16+) and subpopulations of monocytes.

Results: Forty six infants were recruited, 40 preterm and 6 healthy term controls including 11 less than 25 weeks gestation (22+4 to 25 weeks). Increased expression of CD11b on neutrophils and monocytes were seen following LPS administration in all groups. Neutrophil and total monocyte CD11b expression in preterm infants with sepsis was particularly sensitive to LPS, showing a robust response. TLR4 expression appeared similar in all groups, showing slightly lower expression in total monocytes of less than 25 week gestation infants.

Conclusion(s): In preterm infants dysregulated immune responses may play a role in their susceptibility to sepsis especially less than 25 weeks gestation. Understanding the preterm infant's innate immune function may help develop targeted immunomodulatory treatments in the future to improve outcomes.