Modulatory effect of magnesium sulfate on NLRP3 inflammasome expression by human monocytes stimulated in vitro with monosodium urate.

The NLRP3 inflammasome contributes to inflammation in preeclampsia (PE), a hypertensive pregnancy disorder associated with immune imbalance. Magnesium sulfate (MgSO4), the standard therapy for eclampsia, also exhibits anti-inflammatory properties linked to intracellular calcium regulation. This study investigated the modulatory effect of MgSO4 on NLRP3 inflammasome expression in monocytes from 16 healthy non-pregnant women stimulated with monosodium urate (MSU). Monocytes were cultured in vitro with or without MSU and MgSO4. Gene and protein expression of NLRP3, caspase-1, and gasdermin D were assessed by RT-qPCR and flow cytometry. The concentrations of IL-1β, IL-18, TNF-α, and IL-10 in culture supernatants were measured using ELISA. MSU stimulation increased the expression of NLRP3 and its components, confirming the activation of the inflammasome. Treatment with MgSO4 significantly reduced the expression of NLRP3, caspase-1, gasdermin D, IL-1β, and TNF-α, while increasing IL-10 levels. Additionally, MSU induced intracellular calcium elevation, whereas MgSO4 significantly decreased calcium concentration. These findings demonstrate that MgSO4 exerts an immunomodulatory effect on MSU-activated monocytes by downregulating NLRP3 inflammasome activation, pyroptosis, and proinflammatory cytokine production through a calcium-dependent mechanism. This suggests that MgSO4 may contribute to reducing the exaggerated inflammatory response associated with PE, supporting its therapeutic actions beyond seizure prevention.