The roles of vitamin D and its analogs in inflammatory diseases

The discovery of nonclassical actions, other than mineral homeostasis, of 1α,25- dihydroxyvitamin D₃ (1,25D3) has expanded its applications. Among these, its anti-inflammation activity has drawn more and more attention of researchers to investigate its role in regulating the progression of inflammatory diseases. The expression of many inflammation-related genes is regulated by 1,25D3 through vitamin D receptor (VDR) in a large variety of cells including immune cells such as, but not limited to, macrophages, dendritic cells, T helper cells, and B cells. Studies of 1,25D3 in these immune cells have shown both direct and indirect immunomodulatory activities affecting innate and adaptive immune responses. Moreover, 1,25D3 can also exert its anti-inflammation effects through regulating the biosynthesis of pro-inflammatory molecules in the prostaglandin pathway or through nuclear factor kappa light-chain-enhancer of activated B cells (NFκB) by affecting cytokine production and inflammatory responses. These actions of 1,25D3 may explain the associations between vitamin D levels and inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, asthma, type 1 diabetes, and systemic lupus erythematosus. Although several analogs of 1,25D3 have shown potent immunomodulatory or anti-inflammatory activity on immune cell cultures or in animal models, no vitamin D analog has been used in clinical research to treat inflammatory diseases. Here, we review the relationship between vitamin D analogs and inflammation based on observations of immune cells, prostaglandin and NFκB pathways, as well as common inflammatory diseases.