Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1–expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1–dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.
Pietro Presicce, Chan-Wook Park, Paranthaman Senthamaraikannan, Sandip Bhattacharyya, Courtney Jackson, Fansheng Kong, Cesar M. Rueda, Emily DeFranco, Lisa A. Miller, David A. Hildeman, Nathan Salomonis, Claire A. Chougnet, Alan H. Jobe, Suhas G. Kallapur
Schematic of IUI.