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IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation
Pietro Presicce, … , Alan H. Jobe, Suhas G. Kallapur
Pietro Presicce, … , Alan H. Jobe, Suhas G. Kallapur
Published March 22, 2018
Citation Information: JCI Insight. 2018;3(6):e98306. https://doi.org/10.1172/jci.insight.98306.
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Research Article Immunology Reproductive biology

IL-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation

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Abstract

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.

Authors

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

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Figure 6

IL-1R blockade decreased inflammatory markers in amniotic fluid in IA LPS–exposed animals.

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IL-1R blockade decreased inflammatory markers in amniotic fluid in IA LP...
Cytokine concentrations were measured by multiplex ELISA. Prostaglandin (PG) concentrations were measured in lipid extract of amniotic fluid by ELISA. (A) rhIL-1ra significantly decreased LPS-induced IL-6, IL-8/CXCL8, MCP1/CCL2, and PGE2, but not TNF-α or PGF2a levels (Ctrl, n = 16; LPS, n = 11; LPS + rhIL-1ra, n = 6). (B) There was a trend (nonsignificant) in reduced neutrophil counts in AF from rhIL-1ra + LPS– compared with LPS-exposed animals. AF neutrophil counts had high intragroup variability. (C) Compared with amniotic fluid, proinflammatory cytokine levels were lower in both fetal (Ctrl, n = 16; LPS, n = 10; LPS + rhIL-1ra, n = 6) and maternal plasma (Ctrl, n = 10; LPS, n = 10; LPS + rhIL-1ra, n = 6. Note that in dam plasma, these cytokines are low to undetectable, except for IL-8/CXCL8. Data are mean ± SEM, *P < 0.05 between comparators by Mann-Whitney test.

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