The immunological implication of the new vitamin D metabolism

Abstract

Vitamin D is a neuro-hormone regulating calcium-phosphate homeostasis, cell proliferation, and immunomodulation. Exogenous and endogenous vitamin D is inactive, and two hydroxylations are required to produce the active hormone. The first hydroxylation is unique to the liver, while the second step occurs in kidney, brain, lung, prostate, placenta, and immune cells. Kidney-derived calcitriol regulates calcium homeostasis. Active hormone produced by brain and immune cells mediates immune system response; lung calcitriol is involved in fighting respiratory tract infections; finally, prostate and placenta vitamin D regulates cells growth and proliferation within such tissues. Immune modulation by vitamin D includes enhancing innate immune response, attenuating and stimulating Th1 and Th2 cell proliferation, respectively, and promoting self-tolerance. Hypovitaminosis D is a common finding in several autoimmune diseases. It is unclear whether hypovitaminosis D could be a consequence or a cause of autoimmune diseases and whether vitamin D supplementation has an impact on these patients. Moreover, there is no consensus on oral cholecalciferol dosage for supplementation. More interventional studies are required to better define how vitamin D could represent both a causation agent in autoimmunity and a target for therapeutic strategies in autoimmune patients.

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

“…Therefore, vitD deficiency may be a consequence of PAH. However, it is also reasonable that vitD-deficient states may worsen existing immune, metabolic, and cardiovascular dysfunctions [5,6], leading to the development of PAH in predisposed patients or to worse outcomes in patients with existing PAH. With the exception of idiopathic PAH, in all other forms of the disease, there is a factor known to be involved in its etiopathogeny, including mutations, systemic diseases, congenital heart defects, infections, drugs, and toxins.…”

“…It plays a crucial role in the regulation of calcium and phosphorous metabolism, and its deficiency leads to bone diseases [5]. VitD is also involved in cellular growth, metabolism, and innate and adaptive immune responses [5,6]. There is no consensus on the threshold levels for 25(OH)vitD deficiency, its assessment, and its treatment, and clinical practice is inconsistent.…”

Impact of Nutrition on Pulmonary Arterial Hypertension

“…Classically, vitamin D deficiency was related to bone diseases. Currently, because of VDR is found is many tissues, such as immune and cardiovascular cells, vitamin D deficiency has also been related to infection, cancer, and respiratory and cardiovascular diseases [53,55,56]. In fact, vitamin D deficiency has been associated with increased all-cause and cardiovascular mortality [57,58].…”

Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy

“…VD acts by skewing T lymphocytes to Th2 polarization and inhibits Th1 and Th17 lymphocyte activity and proliferation. [46]. The activation of Treg seem to be its main immunological activity.…”