Immunomodulatory effects of vitamin D

    Rafiq, Rachida | VU University Medical Center, Department of Internal Medicine and Endocrinology | 23 augustus 2016 | 7.2.16.123CO (5.1.13.033)

The European Congress on Endocrinology is an annual congress in which the latest developments in basic, translational and clinical research in endocrinology is presented and discussed. During this congress I had the opportunity to present the preliminary results of our pilot trial on the effects of vitamin D supplementation in patients with COPD, and discuss the design of our ongoing trial. Several symposia, debates, oral presentations and poster tours took place during the congress. In this report I will discuss the main findings of studies on the immunological effects of vitamin D.

While vitamin D is classically known for its effects in bone and calcium homeostasis, much attention has been given to a potential role of vitamin D in the immune system in recent years. During the congress, a symposium was held discussing these effects1. A large amount of in vitro studies have been performed assessing a potential role of vitamin D in the immune system. It has been shown that a number of immune cells, such as dendritic cells, macrophages and T-cells, express the vitamin D-receptor (VDR). This suggests that vitamin D can influence the function of these cells. Indeed, it has been shown that activation of this receptor leads to the activation of several gene sets in
immune cells. In macrophages, activation of the receptor leads to triggering and activation of the cell and production of antimicrobial peptides. In T-cells, it has been shown that activation leads to inhibition of the auto-agressive T-cells and proliferation of the regulatory T-cells. Also, activation leads to an inhibition of pro-inflammatory cytokines. The hypothesis that vitamin D is involved in the immune system is further strengthened by the finding that immune cells are able to hydroxylate the inactive form of vitamin D (25-hydroxyvitamin D (25(OH)D)) into the active form (1,25- dihydroxyvitamine D (1,25(OH)2D)). Several animal studies support this hypothesis. However, human trials assessing the effects of vitamin D on the immune system remain inconclusive.

In COPD, a potential immunomodulatory effect might play an important role as patients with COPD often suffer from recurrent respiratory infections and an abnormal inflammatory response of the airways. Vitamin D supplementation might therefore be benefical as it can improve antimicrobial defence on the one hand, and inhibit the excessive auto-inflammatory reaction on the other hand. Up to now, two trials have assessed the effects of vitamin D supplementation in patients with COPD. In one study, performed by Lehouck and colleagues2, no effect of vitamin D supplementation was found on exacerbation rate. However, in a subgroup analysis of severe vitamin D-deficient participants (<25 nmol/L) a reduction of exacerbation rate was found. In a more recent study of Martineau and colleagues3, again no effect of vitamin D supplementation was found in the total study population. In a prespecified subgroup analysis with vitamin D-deficient participants (<50 nmol/L), however, a reduction in exacerbation rate was found. These finding suggest that vitamin D supplementation might only be beneficial in patients with vitamin D deficiency. More trials are
needed to confirm these findings. At the moment, several large trials are ongoing and the first results are expected in a few years.

During the congress several studies were presented assessing the effects of vitamin D in the immune system. In an ex vivo study of Penna Martinez and colleagues4, it was shown that the exposure of T helper cells of patients with type 1 diabetes mellitus to high doses of vitamin D lead to differential gene expression patterns with the upregulation of gene sets associated with tolerogenic fenotypes and downregulation of gene set associated with immunogenic phenotypes. While this study was performed in patients with type I diabetes, one might speculate about potential effects in other auto-inflammatory diseases such as COPD.

Also, several observational studies that studied the association of vitamin D levels with inflammation in human cohorts were presented. In a study of Garcia-Fernandez and colleagues5 vitamin D deficiency was associated with higher CRP levels in a population of obese males. In a study of Ersoy & Akalin6 lower vitamin D levels were related to higher levels of auto-antibodies and inflammatory markers as CRP and erythrocyte sedimentation rate. This was also found in the study of de Remigis and colleagues7. In the latter study, a relationship with season was also found. Although these studies were performed in the general population and patients with auto-immune thyroid disease, this strengthens the hypothesis that vitamin D is related to inflammation and can have clinical implications. This was confirmed by a study of Kumar et al.8 that found a negative association between vitamin D levels and mortality rate in patients with sepsis.

This congress gave me the opportunity to learn about the latest developments in research on vitamin D and immunology. Because of the international character of the congress I was able to meet and discuss with scientists from all over the world. Furthermore, we were able to bring attentio n to our
research on the effects of vitamin D supplementation in patients with COPD.

References:

1 Mathieu C, Vitamin D and immunology, DOI: 10.1530/endoabs.41.S14.1

2 Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J et al.: High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2012, 156: 105-114..

3 Martineau A, James W, Hooper R, Barnes N, Jolliffe D, Greiller C et al.: Vitamin D supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Lancet Respir Med 2014

4 Penna-Martinez M, Hess H, Do¨ring C, Nejatian N, Bogdanou D, Shoghi F et al.: High dose vitamin D treatment regulates the gene expression pattern inT helper cells of type 1 diabetes patients. DOI:10.1530/endoabs.41.GP93

5 Fernandez-Garcia JC, Cardona-Diaz F, Cortes-Salazar CM, Asenjo-Plaza M, Garcıa-Ruiz MC, Varea- Marineto E et al: Vitamin D deficiency is highly prevalent in obesity and is related with BMI and inflammation. DOI: 10.1530/endoabs.41.EP168

6 Ersoy M, Akalın A: 25-Hydroxy vitamin D levels and inflammatory markers in patients with graves disease activation. DOI: 10.1530/endoabs.41.EP971

7 De Remigis A, Tomei G, Lattanzio FM, Occhuzzi U, Natalini MT, Daniele Rapino at al: Inverse relationship between seasonal vitamin D variations and thyroid antibodies (TAb) and TSH . DOI:10.1530/endoabs.41.EP972

8 Kumar S, Gutch M: Correlation of serum vitamin D level with mortality in patients with sepsis. DOI: 10.1530/endoabs.41.EP162
 

Keyword: COPD vitamin D T-cells immune system

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