Impact of Vitamin D on Mast Cell Activity, Immunity and Inflammation

http://pubs.sciepub.com/jfnr/4/1/6/


Abstract


Vitamin D is involved not only in bone metabolism with an endocrine function, but is also an important regulator/mediator of the innate and inductive immune system and inflammation. Vitamin D shows an inhibitory effect of Th1 cells, both T and B cells, reduces polarization of Th0 cells to Th1 cells and inhibits the generation of cytokines/chemokines. Vitamin D3 plays a role in cell differentiation, such as Th1, Th2, Th17 and Treg cells, promotes the augmentation of anti-inflammatory cytokines IL-4 and IL-10 and inhibits the generation of IFN gamma released by Th1 cells. Mast cells, which participate in innate and acquired immunity, are involved in allergic reactions. Their products can decrease the ability of Treg cells to produce the immunosuppressant and anti-inflammatory IL-10. Vitamin D increases the expression of the soluble decoy receptor sST2 which is capable of inhibiting inflammatory effects. Treatment with vitamin D3 provokes the reduction of transcription and translation of IFN-gamma IL-12p40 and TNF exerting an anti-inflammatory action. Vitamin D leads to the regulation of Bcl2 and modulation of intracellular kinase pathways p38 and P13K. Moreover, it is involved in the activation of several pathways, including MAPK and cAMP/PKA, and others. The mechanism of anti-inflammatory actions of vitamin D is not yet clear, however, it is assumed that vitamin D3 binds to its receptor and inhibits the macrophage cytotoxicity and the release of vasoactive compounds in mast cells. The benefits of vitamin D are widespread in literature, however, to better understand its effect, more studies are needed.

1. Introduction

The concept described in this paper is based on our laboratory studies on chemokines during thirty years of experience and a summary of the latest key findings reported in the scientific literature.

Deficiency of vitamin D (rickets) was described by Soranus Ephesius (130 A.D.). In 1882, Sniadecki, in Poland, suggested that rickets was caused by lack of exposure to sunlight. Almost 120 years ago Palm concluded, in an epidemiological study, that the common denominator in rickets in children was lack of exposure to sunlight. In 1922, Sir Edward Mellanby successfully provoked rickets in dogs in absence of sunlight, and in the same year McCollum established that vitamin D is independent of vitamin A. In 1926, Steenbock showed that irradiation of animals as well as foods produced vitamin D2. In the present study, we review the recent data regarding the role of vitamin D in the genesis of inflammation and its relationship with immune cells, including mast cells.

Vitamin D (cholecalciferol; calciferol; ergocalciferol) is an essential fat-soluble compound which functions as a hormone. The conversion of pro-vitamin D into vitamin D in our skin is due to sunlight; in fact, vitamin D is often called the “sunshine vitamin”. The primary function of vitamin D is to enhance the intestinal absorption and metabolization of calcium and phosphorus.

There are several vitamin D isomers and not all are biologically active.


Discussion

Malformation of bones and teeth in children are characteristic of rickets, a vitamin D-deficient disease marked by the under-mineralization of skeletal bones which afflicts a large number of children in tropical countries. This disease could be prevented or cured by exposing children to UV light or feeding them with food containing vitamin D. Therefore, vitamin D (active form: 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3]) is important in assisting the body in its absorption of the minerals calcium and phosphorus, necessary for the growth and development of bones and teeth. In adults, the counterpart of rickets is osteomalacia, which is also due to the insufficient presence of vitamin D and involves the loss of calcium from the bones. This is due to the marked suppression in intestinal calcium absorption and the impairment of calcium balance [1]. There are 6 types of vitamin D: D1, D2, D3, D4, D5 and D6, among which vitamins D2 (ergocalciferol) and D3 (cholecalciferol) are the two major physiologically relevant forms in humans, where vitamin D3 seems to be more effective than vitamin D2. These two vitamins are able to restore the transport of calcium and phosphorus in animals displaying abnormalities and might prevent the exacerbation of inflammatory diseases [2]. It is generally accepted that an insufficient vitamin D status contributes to osteoporosis in the elderly [3]. Vitamin D, provided in the diet or produced in the skin, is absorbed from the intestinal tract in association with fats and requires the presence of bile salts. In the skin, after exposure to UVB rays, 7-dehydrocholesterol is converted into pre-vitamin D3, which is subsequently transformed into vitamin D3. A plateau of daily vitamin D production is reached after only 30 min of u.v. B irradiation [4]. Epidemiologic studies suggest an association between vitamin D deficiency and inflammatory diseases, including atopic diseases, respiratory infections, type 1 diabetes mellitus and asthma [5, 6] (Table 1). However, vitamin D has been found to be the most toxic of all vitamins and an overdose causes nausea, headache and diarrhea, as well as hypercalcemia, a serious and irreversible disease which can lead to calcium deposits in several tissues, including heart and kidneys. For these reasons, large amounts of vitamin D should be avoided [7]. The administration of high-dose vitamin D in patients with arthritis, or other chronic inflammatory diseases, can cause hypercalcemia and does not produce any benefit, therefore it is no longer used [8]. However, vitamin D signal pathway is not only involved in bone metabolism with an endocrine function, but also is an important regulatory mediator of the innate and adaptive immune system and inflammation [9]. It is well documented that vitamin D has a protective role in cancer with a large reduction in the incidence of tumor and also plays a role in a plethora of cellular immune processes [10
continued here: http://pubs.sciepub.com/jfnr/4/1/6/
3. Conclusion

This systematic review is intended to present an update on the physiopathology of inflammation in relation to vitamin D, however, some studies do not confirm the beneficial effects of vitamin D supplementation in subjects with inflammatory diseases, therefore more studies are needed in vitro and in vivo to better understand the effectiveness and safety of vitamin D and its potential role in immune-regulation. These findings have implications for future research even though the mechanism of action of vitamin D is still unclear.

 

I have a mushy brain today, Vicki. Do you have a version for dummies?

I take 5000 units per day for arthritis in my hands and believe you me , when I don't take it, my hands tell me about it.

I know that isn't scientific, purely anecdotal, but I have drank the Vitamin D3 Kool aid.

 

Glad it is helping, just click the image and it summarizes everything in a list, which I think is easier to understand.