Vitamin D and the Immune System: New Perspectives on an Old Theme

Department of Orthopaedic Surgery, Molecular Biology Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Endocrinology and metabolism clinics of North America (Impact Factor: 2.86). 06/2010; 39(2):365-79, table of contents. DOI: 10.1016/j.ecl.2010.02.010
Source: PubMed

ABSTRACT Interaction with the immune system is one of the most well-established nonclassic effects of vitamin D. For many years this was considered to be a manifestation of granulomatous diseases such sarcoidosis, in which synthesis of active 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is known to be dysregulated. However, recent reports have supported a role for 1,25(OH)(2)D(3) in mediating normal function of the innate and adaptive immune systems. Crucially, these effects seem to be mediated via localized autocrine or paracrine synthesis of 1,25(OH)(2)D(3) from precursor 25-hydroxyvitamin D(3), the main circulating metabolite of vitamin D. The ability of vitamin D to influence normal human immunity is highly dependent on the vitamin D status of individuals, and may lead to aberrant response to infection or autoimmunity in those who are lacking vitamin D. The potential health significance of this has been underlined by increasing awareness of impaired vitamin D status in populations across the globe. This article describes some of the recent developments with respect to vitamin D and the immune system, and possible clinical implications.

Download full-text


Available from: Martin Hewison, Sep 03, 2015
1 Follower
  • Source
    • "Administering 25-OH vitamin D 3 (e.g., HyD) as a supplement in the drinking water would serve to bypass the 25-hydroxylation step in the liver, thereby directly providing additional substrate for the synthesis of biologically active 1,25-(OH) 2 vitamin D 3 . Higher circulating levels of 1,25-(OH) 2 vitamin D 3 may in turn modulate the response of the immune system to counteract stress-mediated immunosuppression, inhibit bacterial translocation across the gastrointestinal tract, and attenuate the microbial infection and pathological deterioration of proximal growth plates associated with BCO in broilers and TOC in turkeys (Huff et al., 2000; Baeke et al., 2010; Hewison, 2010; Lagishetty et al., 2010; Zhang et al., 2011; Pastorelli et al., 2013; Morris et al., 2014; Mouli and Ananthakrishnan, 2014). Another potential mechanism is a localized effect of 25- OHD 3 in specific tissues. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial chondronecrosis with osteomyelitis (BCO) is the most common cause of lameness in commercial broilers. Growing broilers on wire flooring provides an excellent experimental model for reproducibly triggering significant levels of lameness attributable to BCO. In the present study we evaluated the efficacy of adding HyD (25-OH vitamin D3) to the drinking water as a preventative/prophylactic treatment for lameness. Broiler chicks were reared on 5 x 10 ft flat wire floor panels within 6 environmental chambers. Three chambers were supplied with tap water (Control group) and the remaining chambers were supplied with HyD (HyD group: 0.06 mL HyD solution/L water; dosing based on the HyD Solution label to provide 33.9 μg 25-OHD3/L) from d 1 through 56. Feed was provided ad libitum and was formulated to meet or exceed minimum standards for all ingredients, including 5,500 IU vitamin D3/kg. Lameness initially was detected on d 28, and the cumulative incidence of lameness on d 56 was higher in the Control group than in the HyD group (34.7 vs. 22.7%, respectively; P = 0.03; Z-test of proportions; chambers pooled). The most prevalent diagnoses for lame birds were osteochondrosis and osteomyelitis (BCO) of the proximal femora (52%) and tibiae (79%), accompanied by minor incidences of tibial dyschondroplasia (0.33%), spondylolisthesis, or kinky back (0.67%), and twisted legs (1%). Broilers that survived to d 56 without developing lameness did not differ in BW when compared by group within a gender. The wire flooring model imposes a rigorous, sustained challenge that undoubtedly is much more severe than typically would be experienced by broilers under normal commercial conditions. Therefore the encouraging response to HyD supplementation in the present study supports the potential for 25-OH vitamin D3 to attenuate outbreaks of lameness caused by BCO in commercial broiler flocks. © 2015 Poultry Science Association Inc.
    Poultry Science 06/2015; 94(8). DOI:10.3382/ps/pev160 · 1.67 Impact Factor
  • Source
    • "Vitamin D receptors may be found on the cell surface of macrophages, dendritic cells, and T-and B-lymphocytes [3]. Vitamin D is essential for the differentiation of monocytes to macrophages or dendritic cells and initiation of T cell response [4] [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels.
    Mediators of Inflammation 01/2015; 2015:181986. DOI:10.1155/2015/181986 · 3.24 Impact Factor
  • Source
    • "cardiovascular events, disorders of glucose metabolism , neurodegenerative diseases, and overall mortality (Pradhan et al. 2001; Il'yasova et al. 2005). There is recent evidence that 25(OH)D is an immune modulator and that 1,25(OH) 2 D, formed in tissues outside of the kidney, can accumulate in the microenvironment of lymphoid organs, where it exerts specific autocrine and/or paracrine cell-specific activities (Hewison 2010; Lauretani et al. 2010). Studies of animal models and cell cultures showed both direct and indirect beneficial immune-modulating effects involving the T cells, B cells, and antigen-presenting cells (dendritic cells and macrophages) resulting in a switch from the Th1/Th17 response to the Th2/Treg profile (Helming et al. 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = -0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = -0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = -0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = -0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.
    European geriatric medicine 08/2014; 36(4):9694. DOI:10.1007/s11357-014-9694-4 · 0.55 Impact Factor
Show more