Magnesium Decreases Inflammatory Cytokine Production: A Novel Innate Immunomodulatory Mechanism

Abstract

MgSO4 exposure before preterm birth is neuroprotective, reducing the risk of cerebral palsy and major motor dysfunction. Neonatal inflammatory cytokine levels correlate with neurologic outcome, leading us to assess the effect of MgSO4 on cytokine production in humans. We found reduced maternal TNF-α and IL-6 production following in vivo MgSO4 treatment. Short-term exposure to a clinically effective MgSO4 concentration in vitro substantially reduced the frequency of neonatal monocytes producing TNF-α and IL-6 under constitutive and TLR-stimulated conditions, decreasing cytokine gene and protein expression, without influencing cell viability or phagocytic function. In summary, MgSO4 reduced cytokine production in intrapartum women, term and preterm neonates, demonstrating effectiveness in those at risk for inflammation-associated adverse perinatal outcomes. By probing the mechanism of decreased cytokine production, we found that the immunomodulatory effect was mediated by magnesium and not the sulfate moiety, and it was reversible. Cellular magnesium content increased rapidly upon MgSO4 exposure, and reduced cytokine production occurred following stimulation with different TLR ligands as well as when magnesium was added after TLR stimulation, strongly suggesting that magnesium acts intracellularly. Magnesium increased basal IκBα levels, and upon TLR stimulation was associated with reduced NF-κB activation and nuclear localization. These findings establish a new paradigm for innate immunoregulation, whereby magnesium plays a critical regulatory role in NF-κB activation, cytokine production, and disease pathogenesis.

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“…Cr, on the other hand, did not show the same ability to neutralize the release of active IL‐1β as did Co. It is previously known that magnesium can decrease the production of pro‐inflammatory cytokines, for example, TNF‐α and IL‐6,49 and our findings that Co reduces a Ti‐induced pro‐inflammatory response are interesting.…”

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“…Помимо этого, магний умень-шает вторичное воспаление, связанное с повреждением мозга, стабилизирует клеточные мембраны и ингибирует свободные радикалы, а также улучшает сердечно-сосу-дистую стабильность [131][132][133]. Исследования на экс-периментальных моделях фокальной ишемии у взрослых грызунов показали весьма обнадеживающие результаты [134].…”

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