{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T06:28:37Z","timestamp":1794119317333,"version":"4.8.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection\/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS\/saline exposure at about 80% gestation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IUI induced a robust expression of\n                      <jats:italic>IL6<\/jats:italic>\n                      mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP.  The major sources of\n                      <jats:italic>IL6<\/jats:italic>\n                      mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP,\n                      <jats:italic>ADAM17<\/jats:italic>\n                      (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and\n                      <jats:italic>IL6R<\/jats:italic>\n                      mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced\n                      <jats:italic>IL6<\/jats:italic>\n                      mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1416162","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T01:27:48Z","timestamp":1717464468000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["IL-1 and TNF mediates IL-6 signaling at the maternal-fetal interface during intrauterine 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