![]() ![]() ![]() Multiple cell types of the innate immune system, including respiratory epithelial cells, macrophages, monocytes, and dendritic cells, possess both the enzyme (CYP27B1) required to convert inactive, circulating 25OHD to active 1,25OHD and its receptor, the vitamin D receptor (VDR). Recent studies indicate that vitamin D has extensive influence on gene expression affecting the immune system and the inflammatory cascade. The growing body of evidence implicating vitamin D as a key component of immune regulation has led to further questions about its mechanisms of action and its therapeutic potential that will require further study. Additionally, we will examine epidemiological studies linking relative vitamin D deficiency to risk of infection, as well as completed and ongoing clinical trials assessing the efficacy of vitamin D supplementation for prevention and treatment of infection. We will briefly review recent studies exploring the role of vitamin D as an immunomodulator, especially as it relates host susceptibility to infection, and identify important gaps in our understanding of these mechanistic pathways. Many of these studies have focused on respiratory disease, although there is now evidence that vitamin D deficiency is associated with systemic infection (see separate article in this issue on vitamin D and sepsis). Given its increasingly recognized role as an immunomodulator, numerous studies have begun to explore the relationship between vitamin D deficiency and the incidence and severity of infection in adults and children. However, the optimum levels of 25OHD considered “sufficient” to optimize vitamin D’s actions on these other signaling pathways are not yet confirmed. Indeed, vitamin D has immunomodulatory effects on both the innate and adaptive immune system, modulates the expression of antimicrobial peptides such as cathelicidin, and influences the inflammatory cascade via NFκB. In addition, there are now clear data that the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25OHD) is a hormone that regulates gene expression in multiple signaling pathways apart from those impacting bone mineral density, specifically those affecting immune function and inflammation. Although controversial, 25OHD levels greater than 30 ng/mL (75 nmol/L) may be required. However, mounting evidence suggests that higher levels may be needed for reported non-skeletal benefits of vitamin D, including optimal immune function. Most experts define frank vitamin D deficiency as 25-hydroxyvitamin D (25OHD) levels less than 20 ng/mL (50 nmol/L), based on bone health outcomes such as prevention of osteoporosis and rickets. The American Academy of Pediatrics (AAP) endorsed the IOM recommendations, which recommends that infants who are formula fed or breastfed meet a daily intake of 400 IU/day. Vitamin D is best known for its influence on bone mineral density, and a daily intake up to 800 IU/day of vitamin D has been recommended by the Institute of Medicine (IOM) to maintain levels optimum for bone health.
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