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 postbirth complications. How chorioamnionitis impacts neonate's developing immune system has not been well defined. METHODS: Blood from extremely preterm infants (≤28 wk gestation) was drawn at the first, second, and fourth week of life. Blood was either left unstimulated or stimulated for 4 h with PMA/ionomycin. mRNA expression of transcription factors in unstimulated cells (RORC, TBET, GATA3, and Forkhead box protein 3 (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 wk 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 ratio were sustained over the 4 wk of follow-up. Leukocytes from infants who developed BPD had increased stimulated and unstimulated IL-4 at the first 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 wk after birth. Infants who later developed BPD did not exhibit a strikingly distinct immune profile.

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates.

Regulatory T-cells (Treg) have a protective role for the control of immune activation and tissue damage. The effects of chorioamnionitis (chorio) on Treg in moderate/late preterm newborns are not known. We hypothesized that infants exposed to chorio would have decreased Treg frequency and/or function. We isolated mononuclear cells from adult peripheral blood and cord blood from term and moderate/late preterm infants who were classified for severity of chorio exposure. Mononuclear cells were analyzed by flow cytometry for Treg frequency and phenotype. Treg suppression of activation of conventional T-cells (Tcon) was also quantified. Treg frequencies were similar in all groups of neonates, but lower than that found in adults. Newborn Treg had a naïve phenotype, with decreased levels of CD45RO, HLA-DR, CD39 and TIGIT compared to adult Treg and chorio did not affect the phenotype. Treg from preterm newborns exposed to severe chorio had higher expression of Ki67 compared to the other groups. Treg from preterm newborns were less suppressive than Treg from adults or term, and the level of suppression was reduced with severe chorio. Relative to term, Treg frequency and phenotype were not affected by prematurity and chorio but their functionality was decreased. Lower Treg activity may contribute to inflammation in newborns that is often associated with chorioamnionitis.