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Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30\u2009min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.<\/jats:p>","DOI":"10.1177\/1753425913488430","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T00:50:59Z","timestamp":1370911859000},"page":"214-224","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs"],"prefix":"10.1177","volume":"20","author":[{"given":"Tate","family":"Gisslen","sequence":"first","affiliation":[{"name":"Division of Neonatology\/Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah H","family":"Hillman","sequence":"additional","affiliation":[{"name":"Division of Neonatology\/Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, 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