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

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. [ABSTRACT FROM AUTHOR]