The Effect of Magnesium Sulfate on Lipopolysaccharide Tolerance in Human Monocytes

Binding of lipopolysaccharide (LPS) to toll-like receptor 4 induces release of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and leads to inflammatory pathologies. An immunosuppression status develops together with LPS-induced inflammation named LPS tolerance, which refers to downregulation of LPS signaling after pre-exposure of LPS, providing protection against hyperactive inflammation. During LPS tolerance, production of cytokines is mitigated, and phenotype of immune cells is altered. Magnesium is a crucial micronutrient, and used as an anti-inflammatory agent in clinical. Though the anti-inflammatory effect of magnesium through inhibiting LPS signaling has been demonstrated, the effect of magnesium on LPS tolerance remains unknown. In this study, we investigated modulation of magnesium sulfate (MgSO 4 ) on LPS tolerance. To induce LPS tolerance, THP-1 cells (a human leukemia monocyte cell line) were stimulated with LPS (200 ng/ml, 2 hours) after pre-exposure of LPS (200 ng/ml, 24 hours) with or without pretreatment of MgSO 4 (20 mM, 24 hours). Proliferation, morphological changes, adherence or TNF-α release, as well as the capacity of migration or phagocytosis were studied. From our results, MgSO 4 mitigated TNF-α release by LPS-tolerant cells. MgSO 4 also strengthened the inhibitory effect of LPS tolerance on proliferation or morphological changes. Besides, MgSO 4 enhanced LPS tolerance-triggered upregulation of migration, but not phagocytosis. In summary, MgSO 4 enhances LPS tolerance and alters activities of LPS-tolerant monocytes. Our findings addressed the role of MgSO 4 in immune system, and also provided evidence for a novel mechanism underlying the anti-inflammatory effect of MgSO 4 .