Magnesium sulfate differentially modulates fetal membrane inflammation in a time-dependent manner

Am J Reprod Immunol. 2018 Jul;80(1):e12861. doi: 10.1111/aji.12861. Epub 2018 Apr 30.

Abstract

Problem: Chorioamnionitis and infection-associated inflammation are major causes of preterm birth. Magnesium sulfate (MgSO4 ) is widely used in obstetrics as a tocolytic; however, its mechanism of action is unclear. This study sought to investigate how MgSO4 modulates infection-associated inflammation in fetal membranes (FMs), and whether the response was time dependent.

Method of study: Human FM explants were treated with or without bacterial lipopolysaccharide (LPS); with or without MgSO4 added either: 1 hour before LPS; at the same time as LPS; 1 hour post-LPS; or 2 hours post-LPS. Explants were also treated with or without viral dsRNA and LPS, alone or in combination; and MgSO4 added 1 hour post-LPS After 24 hours, supernatants were measured for cytokines/chemokines; and tissue lysates measured for caspase-1 activity.

Results: Lipopolysaccharide-induced FM inflammation by upregulating the secretion of a number of inflammatory cytokines/chemokines. Magnesium sulfate administered 1-hour post-LPS inhibited FM secretion of IL-1β, IL-6, G-CSF, RANTES, and TNFα. Magnesium sulfate administered 2 hours post-LPS augmented FM secretion of these factors as well as IL-8, IFNγ, VEGF, GROα and IP-10. Magnesium sulfate delivered 1- hour post-LPS inhibited LPS-induced caspase-1 activity, and inhibited the augmented IL-1β response triggered by combination viral dsRNA and LPS.

Conclusion: Magnesium sulfate differentially modulates LPS-induced FM inflammation in a time-dependent manner, in part through its modulation of caspase-1 activity. Thus, the timing of MgSO4 administration may be critical in optimizing its anti-inflammatory effects in the clinical setting. MgSO4 might also be useful at preventing FM inflammation triggered by a polymicrobial viral-bacterial infection.

Keywords: fetal membranes; infection; inflammation; magnesium sulfate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Caspase 1 / metabolism
  • Chorioamnionitis / metabolism
  • Cytokines / metabolism
  • Extraembryonic Membranes / drug effects*
  • Extraembryonic Membranes / metabolism
  • Female
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Magnesium Sulfate / pharmacology*
  • Pregnancy
  • Premature Birth / prevention & control
  • Time Factors
  • Up-Regulation / drug effects

Substances

  • Cytokines
  • Interleukin-1beta
  • Magnesium Sulfate
  • Caspase 1