Magnesium sulfate reduces bacterial LPS-induced inflammation at the maternal-fetal interface

Objectives: Maternal magnesium sulfate (MgSO ₄) administration exerts anti-inflammatory and fetal neuroprotective effects. Based on the link between placental inflammation and fetal immune responses, we examined the effect of MgSO ₄ on LPS-induced inflammation at the maternal-fetal interface. Study design: In vivo model: Pregnant rats (GD19) were injected intraperitoneally with saline, LPS, or MgSO ₄ plus LPS (n = 6 per group). Rats were euthanized; placentas were assayed for CCL2, IL6, and TNFα and placentas were screened for gene expression. Ex vivo model: Human placental cultures were treated with vehicle, LPS, or MgSO ₄ plus LPS. Supernatants were assayed for CCL2, IL6, and TNFα. In addition, placental cultures were analyzed for inflammation-related gene expression and NFκ B activation. Results: In vivo model: Maternal LPS administration resulted in pro-inflammatory mediator production within the placenta; maternal MgSO ₄ treatment significantly attenuated LPS-induced inflammation. Several placental transcripts (APOE, CCL4, CXCL1, and NFκBIZ) differentially expressed following maternal LPS challenge were counter-regulated by MgSO ₄ treatment. Ex vivo model: LPS promoted human placental inflammation and MgSO ₄ significantly reduced inflammation induced by LPS. MgSO ₄ treatment of human placental explants significantly reversed the expression of numerous genes sensitive to LPS regulation and suppressed LPS-induced NFκB activation. Conclusions: MgSO ₄ administration inhibited placental inflammation during LPS-mediated maternal infection. Several placental inflammatory genes whose expression was regulated by LPS were reversed by MgSO ₄ treatment. Our data support the hypothesis that MgSO ₄ attenuates excessive inflammation at the maternal-fetal interface, which when uncontrolled may compromise neonatal health, including neurologic outcomes.