ABSTRACT More than thirty years ago functions of vitamin D other than its beneficial effects on calcium homeostasis and bone metabolism have been identified, mainly in relation to its anti-proliferative effects on cancer cells. Notably, vitamin D deficiency has been associated with a number of pathological conditions, including infections, autoimmune and allergic diseases. Vitamin D, and its metabolites, are actively involved in the regulation of innate and adaptive immune responses. Vitamin D signals through the vitamin D receptor (VDR), a specific zinc-finger nuclear receptor. The functions of vitamin D are characterized as genomic, mediated through the VDR transcriptional effects inside the cell nucleus, and non-genomic, when the VDR induces rapid signaling, situated on the cell membrane and/or cytoplasm. Emerging evidence supports the notion that vitamin D enhances immunity, providing protection towards pathogens, while, concomitantly, it exerts immunosuppressive effects by preventing the detrimental effects of prolonged inflammatory responses to the host. Still, the precise molecular mechanisms involved in vitamin D’s genomic and non-genomic actions remain incompletely defined. Moreover, it is unclear whether vitamin D actions require the synergistic activation of other mediators, such as nuclear membrane receptors. Understanding the biology of vitamin D and the molecular pathways utilized will pave the way for the design of more effective therapeutic strategies. In this review, we present the recent genomic and non-genomic effects of vitamin D from an immunological perspective with a focus on immune-mediated diseases.
Abstract Introduction: At the turn of the twentieth century, ultraviolet light was successfully used to treat tuberculosis of the skin. Upper respiratory tract infections had been inversely associated with sun exposure. During the last decade, basic scientific research demonstrated that vitamin D has an important anti-infective role. Method: Review of the relevant literature on the influence of vitamin D on innate immunity and respiratory tract infection. Results: Vitamin D is involved in the production of defensins and cathelicidin – antimicrobial peptides that provide a natural defence against potential microbiological pathogens. Vitamin D supplementation increases cathelicidin production. Low vitamin D levels are associated with an increased incidence of upper respiratory tract infections. Conclusions: VitaminDappears to play an important role in the regulation of innate immunity in the upper respiratory tract. Optimal vitamin D levels and appropriate dosing schedules have yet to be determined.
Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or treatment of a wide range of diseases. In this brief review the known effects of vitamin D on immune function are described in relation to respiratory health. Vitamin D appears capable of inhibiting pulmonary inflammatory responses while enhancing innate defence mechanisms against respiratory pathogens. Population-based studies showing an association between circulating vitamin D levels and lung function provide strong justification for randomized controlled clinical trials of vitamin D supplementation in patients with respiratory diseases to assess both efficacy and optimal dosage.
Available data suggest that vitamin D plays a role in controlling inflammation in the lungs. However, to date vitamin D-induced production of cathelicidin has not been shown to have an effect on the burden of either viruses or bacteria. Future work should continue to determine the effects of vitamin D-regulated mechanisms in the lung and the possible role of cathelicidin against different pulmonary pathogens in vivo.
Abstract: Vitamin D metabolizing enzymes and vitamin D receptors are present in many cell types including various immune cells such as antigen-presenting-cells, T cells, B cells and monocytes. In vitro data show that, in addition to modulating innate immune cells, vitamin D also promotes a more tolerogenic immunological status. In vivo data from animals and from human vitamin D supplementation studies have shown beneficial effects of vitamin D on immune function, in particular in the context of autoimmunity. In this review, currently available data are summarized to give an overview of the effects of vitamin D on the immune system in general and on the regulation of inflammatory responses, as well as regulatory mechanisms connected to autoimmune diseases particularly in type 1 diabetes mellitus.
Four types of observations have been used to illustrate the seasonal characteristics of epidemic influenza: (1) The experience of a small population during 28 consecutive years, 1946-74, (2) world influenza outbreaks 1964-75 reported to the World Health Organization, (3) the experience of two widely separated localities at about the same latitude, 1969-74, and (4) the experience of two places at latitudes 300 + on opposite sides of the Equator, 1968-74. The following tendencies are shown. (1) Outbreaks of influenza even in the small community came at approximately the same season almost every year. (2) Outbreaks are globally ubiquitous and epidemic loci move smoothly to and fro across the surface of the earth almost every year in a sinuous curve that runs parallel with the 'midsummer' curve of vertical solar radiation, but lags about six months behind it. Such findings exclude the mediation of seasonal control by any agencies of local distribution, and suggest a direct effect of variations in some component of solar radiation on virus or human host. (3) Antigenic variations in influenza A virus tended to have the same seasonal characteristics as epidemicity. This suggests that epidemicity and virus variation are two facets of one seasonally controlled process. None of these seasonal characteristics can be explained by the current concept of influenzal epidemiology. A new hypothesis recently proposed and recapitulated in the Appendix offers a possible explanation. The primary agency mediating seasonal control remains unidentified.
ABSTRACT Background: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physiciandiagnosed seasonal influenza. Objective: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren. Design: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D3 supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen. Results: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D3 group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D3 compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006). Conclusion: This study suggests that vitamin D3 supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. This trial was registered at https://center.umin.ac.jp as UMIN000001373.
BACKGROUND: Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI. OBJECTIVE: To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI. DESIGN: A prospective birth cohort study was performed in healthy term neonates. Concentrations of 25-hydroxyvitamin D (25-OHD) in cord blood plasma were related to RSV LRTI in the first year of life, defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen. RESULTS: The study population included 156 neonates. Eighteen (12%) developed RSV LRTI. The mean plasma 25-OHD concentration was 82 nmol/L. Overall, 27% of neonates had 25-OHD concentrations 50 nmol/L, 27% had 50-74 nmol/L and only 46% had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy. Concentrations of 25- OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not (65 nmol/L versus 84 nmol/L, P .009). Neonates born with 25-OHD concentrations 50 nmol/L had a sixfold (95% confidence interval: 1.6-24.9; P.01) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations 75 nmol/L. CONCLUSIONS: Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life. Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy. Pediatrics 2011;127:e1513–e1520