The Effects of Magnesium Sulfate on the Inflammatory Response of Placentas Perfused With Lipopolysaccharide: Using the Ex Vivo Dual-Perfused Human Single-Cotyledon Model.

Abstract

Multiple mechanisms have been proposed for the neuroprotective effects of magnesium sulfate (MgSO4). We aimed to examine the effects of lipopolysaccharide (LPS) and MgSO4 on the placental expression of nuclear factor κ light chain enhancer of activated B cells (NF-κB), interleukin (IL) 6, adrenocorticotropic hormone (ACTH), and nitric oxide synthase (NOS); all known to participate in the inflammatory cascade. Placentas were obtained and selected cotyledons cannulated and dually perfused ex vivo. Placentas were perfused with 4 perfusion protocols: culture medium (M-199; controls), LPS (1 μg/mL), MgSO4 (6 g/dL), and LPS + MgSO4. Each perfusion experiment continued for 3 hours. Sixteen perfusion experiments were analyzed, 4 separate placentas were studied for each protocol. The protein levels in the perfused cotyledons were studied by Western blot analysis and compared between the groups. Interleukin 6 levels were studied in the maternal and fetal perfusate. The expression of NF-κB p65, IL-6, ACTH, and NOS proteins levels were significantly increased in placentas perfused with LPS as compared to placentas perfused with M-199, MgSO4 ( P < .01 for all). Placentas perfused with LPS+ MgSO4 had similar proteins levels as in the controls and MgSO4 groups. Lipopolysaccharide significantly increased IL-6 levels in maternal perfusate. In the human placenta, MgSO4 blocks the increase in the proteins levels of NF-κB, IL-6, ACTH, and NOS in response to inflammatory stimuli. Magnesium sulfate attenuates excessive placental inflammatory response. The decrease in placental ACTH levels following perfusion with MgSO4 may point to an additional non-anti-inflammatory mechanism of MgSO4.