Domino effect of hypomagnesemia on the innate immunity of Crohn’s disease patients

Table 1 Key immune effectors for Crohn’s disease inflammatory processes

	Role	Ref.
Toll-like receptors	Their overexpression promotes NF-κB pathway leading to immune intolerance to gut normal flora	[17,24,25,28]
IL-1 TNF-α	Stimulation of intestinal stromal cells to release matrix metalloproteinases leading to mucosal damage	[17,20]
Th1 Th17 cells	Secretion of IFNγ, IL-17 and IL-21 activating macrophages (MØ) and stromal cells to release MMPs	[4,17]
NMDA receptors, SP	Intestinal neuronal inflammation	[21,22]

NF-κB: Nuclear factor-kappa B; IL-1: Interleukin 1; MMPs: Matrix metalloproteinases; TNF: Tumor necrosis factor; IFN: Interferon; Th1: T helper 1; NMDA: N-methyl-D-aspartic acid; SP: Substance P.

Table 2 Magnesium and inflammation

	Role	Ref.
NF-κB Pathway	Inhibition of NF-κB p65 phosphorylation and stabilization of IκB protein	[29,39]
NMDA receptors, SP	Low magnesium enhances calcium influx through NMDA receptors	[12,38]
Neutrophilic oxidative stress	Increased levels of superoxide anions and nitric oxide in magnesium deficiency	[12]
Gut microbiota	Low magnesium changes the composition and intestinal permeability	[43]

NF-κB: Nuclear factor-kappa B; SP: Substance P; NMDA: N-methyl-D-aspartic acid; IκB: Inhibitory kappa B.