The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer

Abstract

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status.

Figure 1

Metabolism and effects of VitD. VitD can be obtained from food or from synthesis in the skin under exposure to light. The precursor is hydroxylated cytochrome P450 25-hydroxylase enzymes CYP27A1 and/or CYP2R1 and subsequently by the cytochrome P450 enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) and converted to the bioactive 1,25-(OH)₂D₃, which has role in Ca and bone metabolism and, in addition, in several other biological processes. Of note, bioactive 1,25-(OH)₂D₃ can also be generated in lung epithelia cells and monocytes/macrophages.