7. Vitamin D and immunomodulation

Vitamin D is involved in modulation of immune responses and has an important role in some autoimmune diseases like multiple sclerosis, diabetes mellitus, psoriasis, systemic lupus erythematosus (SLE), RA, etc. [31]. The biological effects or immunomodulation is mediated by the vitamin D receptor (VDR) which belongs to the nuclear hormone receptor family and is expressed in most cell types including macrophages, dendritic cells, B and T lymphocytes, and neutrophils [31, 32].

Along with the modulatory effects on T and B cell functions, VDR agonists inhibit the differentiation and maturation of DCs, thus influencing the function of DCs and promoting tolerogenic properties that favor the induction of regulatory T cells. VDR also downregulate expression of the costimulatory molecules CD40, CD80, and CD86, decrease production of IL-12, and increase production of IL-10. The inhibition of DC differentiation and maturation and production of proinflammatory mediators play an important role in the immunoregulatory activity of 1,25(OH)2D3 [33, 34].

1,25(OH)2D3 also plays an important role in the maintenance of B cell homeostasis. It has potent effects on functions of B cell, including induction of apoptosis and inhibition of proliferation, generation of memory B cells, plasma cell differentiation, and immunoglobulin production [35].

According to Grant, there is evidence in support of vitamin D reducing the risk of many autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus. However, evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension, and stroke is weak [36].

Vitamin D in Rheumatic Diseases: Interpretation and Significance DOI: http://dx.doi.org/10.5772/intechopen.88677

### 8. SLE

6. Immune system and vitamin D: Vitamin D is a potent immunomodulator. 1,25 (OH)2D decreases the maturation of dendritic cells (DCs) decreasing their ability to present antigen and to activate T cells [23]. Furthermore, it

suppresses production of IL-12 (important for Th1 development), IL-23, and IL-6 (important for Th17 development) [24]. But, there is no any approved vitamin D drug for immune modulation [1]. Studies have suggested an association of vitamin D with autoimmune diseases like multiple sclerosis [25]

7.Cardiovascular disease and vitamin D: There is an inverse relationship between vitamin D deficiency and risk of heart disease, myocardial infarction, and early

inflammation, proliferation of vascular smooth muscle cells, insulin resistance,

remodeling. All of these are associated with increased risk of ischemic heart

death. Low vitamin D causes increased parathyroid hormone release,

thrombogenicity, dyslipidemia, and progressive extracellular matrix

8.Diabetes mellitus and vitamin D: Vitamin D deficiency is associated with insulin resistance. 1,25(OH)2D promotes increased lipogenesis and decreased lipolysis. The pancreatic B cell expresses the VDR, and 1,25(OH)2D promotes

9.Neurological disorder and vitamin D: Vitamin D plays an important role in brain development as it has effects on neuronal proliferation, differentiation,

Vitamin D is involved in modulation of immune responses and has an important role in some autoimmune diseases like multiple sclerosis, diabetes mellitus, psoriasis, systemic lupus erythematosus (SLE), RA, etc. [31]. The biological effects or immunomodulation is mediated by the vitamin D receptor (VDR) which belongs to the nuclear hormone receptor family and is expressed in most cell types including macrophages, dendritic cells, B and T lymphocytes, and neutrophils

Along with the modulatory effects on T and B cell functions, VDR agonists inhibit the differentiation and maturation of DCs, thus influencing the function of DCs and promoting tolerogenic properties that favor the induction of regulatory T cells. VDR also downregulate expression of the costimulatory molecules CD40, CD80, and CD86, decrease production of IL-12, and increase production of IL-10. The inhibition of DC differentiation and maturation and production of pro-

inflammatory mediators play an important role in the immunoregulatory activity of

1,25(OH)2D3 also plays an important role in the maintenance of B cell homeostasis. It has potent effects on functions of B cell, including induction of apoptosis and inhibition of proliferation, generation of memory B cells, plasma cell differen-

According to Grant, there is evidence in support of vitamin D reducing the risk of many autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus. However, evidence for rheumatoid arthritis, osteoarthritis, type 2

disease, myocardial infarction, and early death [27, 28].

and asthma [26].

Fads and Facts about Vitamin D

insulin secretion [29].

[31, 32].

86

1,25(OH)2D3 [33, 34].

migration, and apoptosis [30].

7. Vitamin D and immunomodulation

tiation, and immunoglobulin production [35].

diabetes mellitus, hypertension, and stroke is weak [36].

Vitamin D deficiency is quite prevalent in SLE patients which may be attributable to various reasons. Avoidance of sunshine, photoprotection, renal insufficiency, and the use of medications which alter the metabolism of vitamin D or downregulate the functions of the vitamin D receptor like glucocorticoids, anticonvulsants, antimalarials, and the calcineurin inhibitors are some of the causes of VDD as shown in Figure 2 [37]. In a study by Toloza, vitamin D insufficiency was found in 66.7% and deficiency in 17.9% of SLE patients [38]. The frequency varied in different studies: Saudi Arabia (89.7%) [39], Norway (82%) [40], Poland (71%) [41], Hong Kong (27%) [42], and the United States (20%) [43]. Low serum vitamin D levels were related to cumulative glucocorticoid dose [38]. Corticosteroids accelerate the catabolism of 25(OH)D and 1,25(OH)2D and have a significant role in secondary osteoporosis [44]. Patients taking corticosteroids often require higher daily doses of vitamin D to maintain adequate levels [45]. Similarly, a commonly used antimalarial, hydroxychloroquine (HCQ), inhibits conversion of 25(OH)D to 1,25(OH)2D leading to low levels of vitamin D [46].

A review by Sakthiswary demonstrated a substantial evidence in support of the association between vitamin D levels and SLE disease activity. However, vitamin D level is not associated with organ damage [47]. A study by Suzan showed a significant negative correlation that existed between 25(OH)D and anti-dsDNA and a positive correlation between 25(OH)D levels and C4 [48]. Another similar study showed a significant negative correlation between the serum concentration of vitamin D and the standardized values of disease activity scores as measured by the SLEDAI-2K and ECLAM scales [49]. An Australian study showed that low vitamin D

#### Figure 2.

The two-sided relation between vitamin D and SLE showing that low levels of vitamin D resulted from SLE and SLE complications that come from vitamin D deficiency [37].

was associated with a higher disease activity and an increase in serum vitamin D was associated with reduced disease activity over time [50]. Improving vitamin D status may improve other common manifestations as well, such as fatigue [51] and cognitive dysfunction [52].

11. Undifferentiated arthritis

DOI: http://dx.doi.org/10.5772/intechopen.88677

Author details

89

Binit Vaidya\* and Shweta Nakarmi

provided the original work is properly cited.

National Center for Rheumatic Diseases, Kathmandu, Nepal

\*Address all correspondence to: drbinitvaidya@yahoo.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

factors of disease progression to RA [76, 78].

Vitamin D in Rheumatic Diseases: Interpretation and Significance

Significant association has been reported between vitamin D deficiency and nonspecific musculoskeletal pain, arthralgias, or undifferentiated arthritis [74, 75]. A positive correlation of VDD with undifferentiated arthritis [76] and early inflammatory arthritis [77] has been observed. It has also shown VDD as one of the risk
