Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance

Maureen L. Kim, Caroline Maloney, Natalia Klimova, Ellen Gurzenda, Xinhua Lin, Yuko Arita, Treasure Walker, Melissa J. Fazzari, Nazeeh Hanna

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Article numbere13080
JournalAmerican Journal of Reproductive Immunology
Issue number2
StatePublished - Feb 2019
Externally publishedYes


  • LPS
  • endotoxin tolerance
  • inflammation
  • placenta
  • pre-term labor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology


Dive into the research topics of 'Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance'. Together they form a unique fingerprint.

Cite this