Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D)

Created November 2017

Modulation of inflammatory and immune responses by vitamin D

Journal of AutoimmunityJuly 2017 https://doi.org/10.1016/j.jaut.2017.07.007

Francesco Colotta a *, Birger Jansson a, Fabrizio Bonelli b

a DiaSorin SpA, Saluggia, VC, Italy b DiaSorin Inc, Stillwater, MN, USA

* This study feels that Calcitriol would be a better measure than current vitamin D blood test * VitaminDWiki feels that it would be even better to measure the active vitamin D actually getting into the cells, as this would include the limiting affects of many genes * Unfortunately, as of Nov 2017, there appears to be no means to measure the cellular vitamin D See the left-hand column for many studies of each of the health problems Calcitriol category listing has items along with related searches 1. Genetics category listing contains the following {include}

📄 Download the PDF via SciHub from VitaminDWiki

Vitamin D (VitD) is a prohormone most noted for the regulation of calcium and phosphate levels in circulation, and thus of bone metabolism. Inflammatory and immune cells not only convert inactive VitD metabolites into calcitriol, the active form of VitD, but also express the nuclear receptor of VitD that modulates differentiation, activation and proliferation of these cells. In vitro, calcitriol upregulates different anti-inflammatory pathways and downregulates molecules that activate immune and inflammatory cells. Administration of VitD has beneficial effects in a number of experimental models of autoimmune disease. Epidemiologic studies have indicated that VitD insufficiency is frequently associated with immune disorders and infectious diseases, exacerbated by increasing evidence of suboptimal VitD status in populations worldwide. To date, however, most interventional studies in human inflammatory and immune diseases with VitD supplementation have proven to be inconclusive. One of the reasons could be that the main VitD metabolite measured in these studies was the 25-hydroxyVitD (25OHD) rather than its active form calcitriol. Although our knowledge of calcitriol as modulator of immune and inflammatory reactions has dramatically increased in the past decades, further in vivo and clinical studies are needed to confirm the potential benefits of VitD in the control of immune and inflammatory conditions.

Partial Table of Contents

Forms VitD, Synthesis of the active metabolite calcitriol, VitD receptors, Physiological activities of VitD, VitD levels and sufficiency, VitD dietary allowance, VitD deficiency, Methods to measure circulating VitD, Modulation of immune and inflammatory cells by calcitriol, Dendritic cells (DCs), Monocytes and macrophages, B cells, T cells, CD4+ T cells, Cytotoxic CD8+ T cells, Unconventional T cells, Innate lymphoid cells (ILC),

  • VitD in inflammatory diseases,

  • Asthma (Tables 2 and 3),

  • Inflammatory bowel disease (IBD),

  • Respiratory tract infections (RTI) (Table 4),

  • VitD and autoimmunity, Biological plausibility,

Experimental models of autoimmune diseases,

  • Multiple sclerosis (MS) (Table 5),

  • Rheumatoid Arthritis (RA) (Tables 6 and 7),

  • Type 1 Diabetes (T1D),

  • Systemic Lupus Erythematosus (SLE) (Tables 8 and 9),

  • Psoriasis

Summary table on effects of calcitriol on immune and inflammatory cells

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Concluding remarks - clipped from PDF

There is a growing body of evidence that VitD, especially its active metabolite, plays a key role in modulating the physiological activity of the immune system. This emergent role has stimulated a florid line of research aimed at associating the level of VitD with pathological situations wherein the immune system may be altered, such as in autoimmunity and inflammation.

In these studies, 25OHD, the actual precursor of the active hormone calcitriol , is what has been routinely measured, circulating in the blood at ng/mL concentrations. This measurement, performed with either LCMS or immunoassay, has recently become significantly more reliable consequent to marked gains in com- mutability enabled by the broad acceptance of and adherence to an international standardization program.

Several epidemiological studies of observational nature have been conducted to correlate circulating levels of 25OHD with autoimmune and inflammatory disease parameters. Overall, the studies have shown an inverse relationship between 25OHD and the clinical manifestations of a given disease. At the same time, circulating levels of sufficiency/insufficiency have been proposed by major medical organizations such as the Institute of Medicine (IOM) [43] and Endocrine Society [51], with different thresholds belying slightly different demographic perspectives. While associations with the disease are strong and potential mechanisms tractable, still the role of the VitD in inflammation and autoimmunity deserve large and well controlled clinical studies.

VitD supplementation has not always diminished the severity of clinical manifestations. A likely explanation of these perceptually negative outcomes, is that the majority of these studies attempted correlations with measured levels of precursor 25OHD and not the active hormone per se. Testing circulating levels of calcitriol might support the establishment of more robust disease correlates between the biologically active VitD metabolite and pathological conditions.

Tags: Autoimmune Breathing Calcitriol Diabetes Gut Immunity Lupus Multiple Sclerosis Rheumatoid Arthritis Vit D Receptor