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



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).



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.



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.
Department of Pediatrics, Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Courtney M
CM
Jackson
Department of Pediatrics, Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Casey B
CB
Wells
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Meredith E
ME
Tabangin
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Jareen
J
Meinzen-Derr
Department of Pediatrics Division of Neonatology/Pulmonary Biology, the Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
Alan H
AH
Jobe
Department of Pediatrics, Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Claire A
CA
Chougnet
D001997:Bronchopulmonary Dysplasia / Q000097:blood / Q000276:immunology*; D002821:Chorioamnionitis / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007249:Inflammation; D008297:Male; D011247:Pregnancy; D058504:Th17 Cells / Q000166:cytology; D014157:Transcription Factors / Q000097:blood
D016207:Cytokines; D014157:Transcription Factors