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 (Mg SO 4 ) is widely used in obstetrics as a tocolytic; however, its mechanism of action is unclear. This study sought to investigate how Mg SO 4 modulates infection‐associated inflammation in fetal membranes ( FM s), and whether the response was time dependent. Method of Study Human FM explants were treated with or without bacterial lipopolysaccharide ( LPS ); with or without Mg SO 4 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 ds RNA and LPS , alone or in combination; and Mg SO 4 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 TNF α. Magnesium sulfate administered 2 hours post‐ LPS augmented FM secretion of these factors as well as IL ‐8, IFN γ, VEGF , GRO α 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 ds RNA 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 Mg SO 4 administration may be critical in optimizing its anti‐inflammatory effects in the clinical setting. Mg SO 4 might also be useful at preventing FM inflammation triggered by a polymicrobial viral‐bacterial infection.