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Vitamin D: An Evolving Star

By: Peter T. Pugliese, MD
Posted: June 29, 2009, from the July 2009 issue of Skin Inc. magazine.
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Calcitonin is a 34-amino acid peptide hormone that is a major compound for lowering serum calcium by its action on the skeleton. Increased levels of calcium, or hypercalcemia, cause calcification of soft tissues, such as the kidney, heart, aorta and intestine, resulting in organ failure and death. The deactivation of the parathyroid gland is an important step to control high calcium levels. When calcium levels are high, it triggers the activation of the parafollicular cell (C cells) of the thyroid to secrete the hormone calcitonin. Also, calcitonin acts on osteoclasts and osteocytes to reduce the calcium-mobilizing activity and deactivation of the calcium coming from the skeleton. Although other actions of calcitonin have been described in both the kidney and intestine, the most important is the regulation of serum calcium that occurs in the skeleton.6

Vitamin D, the immunomodulator

Vitamin D, when activated, has many important roles in helping the immune system function well. It does this by binding to nuclear VDR, present in most immune cell types—both innate and adaptive. The VDR is expressed in monocytes and in activated macrophages, dendritic cells<sup>b</sup> (DC), natural killer (NK) cells, and T and B cells. This means that vitamin D has potent antiproliferative, pro-differentiative and immunomodulatory functions,including both immune-enhancing and immuno-suppressive effects.7

When vitamin D binds to the receptor, it increases the activity of NK cells and enhances the phagocytic activity of macrophages. Vitamin D deficiency tends to increase the risk of infections, such as influenza and tuberculosis.8

For example, a study in 1997 showed that Ethiopian children with rickets, or vitamin D deficiency, were 13 times more likely to get pneumonia than children without rickets.9 Vitamin D, when activated, has been shown to affect DC maturation, differentiation and migration, which relates to inhibition of DC-dependent T cell activation, the final result being immunosuppression.10

The significance of these immunoregulatory properties indicate that the substances with the potential to activate vitamin D may have therapeutic applications in the treatment of inflammatory diseases (rheumatoid arthritis, psoriatic arthritis), dermatological conditions (psoriasis, actinic keratosis), osteoporosis, cancers (prostate, colon, breast, myelodysplasia, leukemia, squamous cell carcinoma and basal cell carcinoma), autoimmune diseases (systemic lupus erythematosus), type I diabetes, central nervous systems diseases (multiple sclerosis), and in preventing organ transplant rejection.8