Vitamin D and immunomodulation: Is it time to change the reference values?

The term "vitamin D" refers to two chemical compounds - ergosterol, or vitamin D2, and cholecalciferol, or vitamin D3. Active vitamin D3 is correctly regarded as a neurohormone due to its pleiotropic biological activities. Although the relation between vitamin D and calcium-phosphorus metabolism has never been discussed, the knowledge on many other roles vitamin D plays is growing fast. Briefly, vitamin D immunomodulation includes attenuation and stimulation of Th1 and Th2 cell proliferation, respectively. Similarly, vitamin D can induce or inhibit the synthesis, secretion, and release of anti- inflammatory (IL- 4 and IL-10) and pro-inflammatory (IL-1, TNF-α, IFN-γ) cytokines, respectively. Redefining vitamin D reference values seems to be either a critical or urgent issue. There is not so far a univocal consensus on the reference values of vitamin D status, mainly because of such reference value rates on the basis of the parathyroid hormone (PTH) plasma response. The optimal serum concentration of vitamin D has been considered to lead not to a PTH elevation. Such criterion is clearly resulted from a partial knowledge of the biology of vitamin D so that it can be considered at least obsolete. Based on the distribution of vitamin D levels among healthy individuals and inflammatory/autoimmune patients, an appropriate review of vitamin D reference values is required, following adequate standardization and harmonization of the cut-off, as well as taking into account the ethnic/cultural/geographical features influencing vitamin D status.