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

Objectives:

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.

Methods:

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.

Results:

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.

Conclusions:

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.