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Title: Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance. Author: Kim ML, Maloney C, Klimova N, Gurzenda E, Lin X, Arita Y, Walker T, Fazzari MJ, Hanna N. Journal: Am J Reprod Immunol; 2019 Feb; 81(2):e13080. PubMed ID: 30586203. Abstract: PROBLEM: Placental infection induces increased levels of pro-inflammatory cytokines, which have been implicated in the pathogenesis of pre-term labor. Endotoxin tolerance is a phenomenon in which exposure to a dose of endotoxin makes tissue less responsive to subsequent exposures. The objective of our study was to determine whether repeated exposure to endotoxin will induce a tolerant phenotype in normal human second-trimester placental tissue. METHODS OF STUDY: Human second-trimester placental explants from elective termination of pregnancy were cultured and exposed to endotoxin (LPS). After 24 hours, the media was collected for analysis, and the explants were re-exposed to LPS after adding fresh media for another 24 hours. This process was repeated for a total of 4 LPS doses. The media was collected from each day and analyzed for cytokine levels. RESULTS: The first LPS treatment stimulated the secretion of the pro-inflammatory cytokines IL-1β and TNF-α. However, their production was significantly diminished with repeated LPS doses. Production of the anti-inflammatory cytokines, IL-1ra and IL-10, was also stimulated by the first LPS treatment, but secretion was more gradually and moderately decreased with repeated LPS doses compared to the pro-inflammatory cytokines. The ratios of the anti-inflammatory/pro-inflammatory mediators (IL-1ra/IL-1β and IL-10/TNF-α) indicate a progressively more anti-inflammatory milieu with repeated LPS doses. CONCLUSION: Repeated LPS exposure of human second-trimester placental tissues induced endotoxin tolerance. We speculate that endotoxin tolerance at the maternal-fetal interface will protect the fetus from exaggerated inflammatory responses after repeated infectious exposure.[Abstract] [Full Text] [Related] [New Search]