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 journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere13080
JournalAmerican Journal of Reproductive Immunology
Volume81
Issue number2
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

Fingerprint

Endotoxins
Lipopolysaccharides
Cytokines
Second Pregnancy Trimester
Interleukin 1 Receptor Antagonist Protein
Anti-Inflammatory Agents
Interleukin-1
Interleukin-10
Fetus
Mothers
Phenotype
Pregnancy
Infection

Keywords

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

ASJC Scopus subject areas

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

Cite this

Kim, M. L., Maloney, C., Klimova, N., Gurzenda, E., Lin, X., Arita, Y., ... Hanna, N. (2019). Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance. American Journal of Reproductive Immunology, 81(2), [e13080]. https://doi.org/10.1111/aji.13080

Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance. / Kim, Maureen L.; Maloney, Caroline; Klimova, Natalia; Gurzenda, Ellen; Lin, Xinhua; Arita, Yuko; Walker, Treasure; Fazzari, Melissa J.; Hanna, Nazeeh.

In: American Journal of Reproductive Immunology, Vol. 81, No. 2, e13080, 01.02.2019.

Research output: Contribution to journalArticle

Kim, ML, Maloney, C, Klimova, N, Gurzenda, E, Lin, X, Arita, Y, Walker, T, Fazzari, MJ & Hanna, N 2019, 'Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance', American Journal of Reproductive Immunology, vol. 81, no. 2, e13080. https://doi.org/10.1111/aji.13080
Kim, Maureen L. ; Maloney, Caroline ; Klimova, Natalia ; Gurzenda, Ellen ; Lin, Xinhua ; Arita, Yuko ; Walker, Treasure ; Fazzari, Melissa J. ; Hanna, Nazeeh. / Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance. In: American Journal of Reproductive Immunology. 2019 ; Vol. 81, No. 2.
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