Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis.
During the progression of Mg deficiency in a rodent model, we have observed dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk on a Mg-deficient diet. Sequential analyses of these cytokine changes in the serum of rats revealed an initial rise at day 12, followed by a major elevation in all three cytokine levels by day 21. Of greater interest was an early peak in the serum level of the neuropeptide substance P after only 5 days on the diet. This "neuronal" tachykinin is thought to be released from neural tissues, and it is known to stimulate production of certain cytokines, including IL-1, IL-6, and TNF-alpha. In addition, there was a concomitant increase in histamine levels, which may have resulted from stimulation and degranulation of mast cells by substance P. Thus we hypothesize that the release of substance P may be the earliest pathophysiological event leading to stimulation of the inflammatory cytokines, which may then stimulate the free radical mechanisms of injury previously confirmed by our work.
Weglicki
W B
WB
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Phillips
T M
TM
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000502:physiology*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008275:Magnesium Deficiency / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009424:Nervous System Physiological Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000097:blood; D013997:Time Factors
D016207:Cytokines; D013373:Substance P