Pro-inflammatory immune responses in leukocytes of premature infants exposed to maternal chorioamnionitis or funisitis

BACKGROUND: Acute chorioamnionitis contributes to premature birth, and is associated with post-birth complications. How chorioamnionitis impacts neonate’s developing immune system has not been well defined. METHODS: Blood from extremely preterm infants (≤28 weeks gestation) was drawn at the 1(st), 2(nd), and 4(th) week of life. Blood was either left unstimulated or stimulated for 4 hours with PMA/ionomycin. mRNA expression of transcription factors in unstimulated cells (RORC, TBET, GATA3, FOXP3) and inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, and IL-6) in unstimulated and stimulated cells were analyzed. Data were analyzed based on the diagnosis of chorioamnionitis, funisitis and bronchopulmonary dysplasia (BPD). RESULTS: At 1 week of life, exposure to funisitis, but not maternal chorioamnionitis was associated with an increased expression of RORC and RORC/FOXP3 ratio. These increases in RORC and RORC/FOXP3 ration were sustained over the 4 weeks of follow-up. Leukocytes from infants who developed BPD had increased stimulated and unstimulated IL-4 at the 1(st) week of life, but these increases were not sustained over time. In contrast, infants with mild BPD had a sustained decrease in stimulated IL-2. CONCLUSION: Chorioamnionitis exposure, in particular to funisitis, lead to enhanced Th17-like responses that persist for 4 weeks after birth. Infants who later developed BPD did not exhibit a strikingly distinct immune profile.