Immunoregulation by neuropeptides in magnesium deficiency: ex vivo effect of enhanced substance P production on circulating T lymphocytes from magnesium-deficient mice

• Published in: Magnesium research Vol. 9; no. 1; p. 3
• Main Authors: Weglicki, W B, Dickens, B F, Wagner, T L, Chmielinska, J J, Phillips, T M
• Format: Journal Article
• Language: English
• Published: England 01-03-1996
• Subjects: Animal Feed; Animals; Cytokines - analysis; Cytokines - biosynthesis; Cytokines - secretion; Electrophoresis, Capillary; Enzyme-Linked Immunosorbent Assay; Magnesium - administration & dosage; Magnesium - blood; Magnesium Deficiency - blood; Magnesium Deficiency - immunology; Magnesium Deficiency - physiopathology; Male; Mice; Mice, Inbred BALB C; Receptors, Neurokinin-1 - biosynthesis; Receptors, Neurokinin-1 - metabolism; Substance P - blood; Substance P - metabolism; Substance P - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors
• ISSN: 0953-1424

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.