Poster Presentation 6th Australian Health and Medical Research Congress 2012

Preterm neonates display a relative decrease in innate anti-inflammatory capacity following TLR stimulation.   (#434)

Natalie Aboustate 1 , Michael J Stark 1 , Vicki L Clifton 1 , Nicolette A Hodyl 1
  1. Robinson Institute, University of Adelaide School of Paediatrics and Reproductive Health, Elizabeth Vale, SA, Australia

Some but not all preterm neonates develop inflammatory related conditions in the neonatal period, including sepsis and nocosomial infections. The reasons for this differential response are unclear, but may be related to differences in the ability of cord blood cells to respond to pathogens. In order to explore this, we aimed to characterise the responses of neonatal term and preterm cord blood, following exposure to a variety of Toll-Like Receptor (TLR) agonists including Peptidoglycan TLR2; Poly I:C TLR3; Lipopolysaccharide TLR4; Imiquimod TLR7; CpG oligonucleotide TLR9. Cord blood was stimulated for 6 hours and cytokine levels were measured by multiplex ELISA. Data was analysed according to gestational age and mode of delivery.

Results: The production of IL10, IL1RA and MCP-1 in preterm cord blood was significantly lower compared to term neonates following stimulation by all TLR agonists (p<0.05 in all cases). Similarly, IL1β, GMCSF and IL12 were significantly lower compared to term neonates following TLR3, TLR7 and TLR9 stimulation (p<0.05 in all cases), indicating an inability to mount a pro-inflammatory cytokine response to viral particles. No gestational age differences in sCD40L and IL2 were observed following TLR stimulation. Compared to those born vaginally, neonates delivered by Caesarean section produced lower levels of IL10 post TLR7 and TLR9 stimulation, but higher levels post TLR4 stimulation. Non-labour delivery was also associated with decreased IL1β and increased IL-1RA post TLR4 and TLR3 stimulation, indicating that exposure to labour primes the neonatal innate immune response.

Conclusion: Preterm neonates may be more prone to inflammatory conditions in the neonatal period due to a fundamental immaturity in their innate immune response, leaving them unable to recognise and therefore respond to pathogens appropriately. This was particularly evident when stimulated with viral mimetics. Studies are continuing in our laboratory to identify antecedents and elucidate further the mechanisms leading to an immature innate immune response.