Immunoregulation by neuropeptides in magnesium deficiency: ex vivo effect of enhanced substance P production on circulating T lymphocytes from magnesium-deficient mice.
The first week of dietary magnesium deficiency in rodent models is characterized by the induction of raised levels of neuropeptides (substance P [SP] and calcitonin gene related peptide [CGRP]), followed shortly thereafter by inflammatory cytokine release. Since neuropeptides participate in neurogenic inflammation, we have proposed that the neurogenic inflammatory response plays a role in the pathology of magnesium deficiency. However, the association between the early neuropeptide release and the subsequent pathology in this model remains unclear. Peripheral blood T lymphocytes were obtained from Balb/c mice fed a magnesium-deficient diet (approximately 1.8 mmol Mg/kg), or the same diet supplemented with 20 mmol MgO/kg. These cells were incubated in medium containing 10(-10) to 10(-5) M SP, after which the cells were examined for expression of SP receptors and the supernatants were collected and examined by immunochemical techniques for the presence of T lymphocyte associated cytokines. SP stimulation induced the secretion of interleukin (IL)-2, 4, 5, 10, 12, 13 and interferon-gamma (IFN-gamma). T lymphocytes from magnesium-deficient animals, when compared to magnesium-sufficient ones, secreted increased levels of these cytokines. The secretion of these cytokines was maximal at either 5 days (IL-4, IL-5) or 7 days (II-2, IL-10, and IFN-gamma) of magnesium deficiency. This increased sensitivity to SP appears to be related to an increased expression of SP receptors on the surface of T lymphocytes during the first week of magnesium deficiency. These data indicate that SP released early during magnesium deficiency exerts a regulatory role on T lymphocyte cytokine production, especially those cytokines regulating mast cell and immune responses leading to the onset of an immunopathological state.
Weglicki
W B
WB
George Washington University Medical Center, Department of Medicine, Washington, DC 20037, USA.
Dickens
B F
BF
Wagner
T L
TL
Chmielinska
J J
JJ
Phillips
T M
TM
D000821:Animal Feed; D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D019075:Electrophoresis, Capillary; D004797:Enzyme-Linked Immunosorbent Assay; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood; D008275:Magnesium Deficiency / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis / Q000378:metabolism; D013373:Substance P / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D018040:Receptors, Neurokinin-1; D013373:Substance P; D008274:Magnesium