A role for vitamin D in the regulation of immune function was first proposed after the identification of Vitamin D Receptors in lymphocytes. It has since been recognized that the active form of vitamin D, 1α,25(OH)2D3, has direct affects on naïve and activated helper T cells, regulatory T cells, activated B cells and dendritic cells. There is a growing body of literature linking vitamin D (serum 25(OH)D, oral intake and surrogate indicators such as latitude) to various immune-related conditions, including allergy, although the nature of this relationship is still unclear. This review explores the findings of epidemiological, clinical and laboratory research, and the potential role of vitamin D in promoting the inappropriate immune responses which underpin the rise in a broad range of immune diseases.

Lower vitamin D status at birth and during infancy has been associated with increased incidence of eczema and food allergies. The aim of this study was to investigate the effect of early infancy vitamin D supplementation on allergic disease outcomes in infants at “hereditary risk” of allergic disease, but who had sufficient vitamin D levels at birth. Here, we report the early childhood follow-up to 2.5 years of age of “high-risk” infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36–40 weeks) maternal 25-hydroxyvitamin D levels needed to be ≥50 nmol/L. Infants were randomized to either oral vitamin D supplementation of 400 IU/day (n = 97) or a placebo (n = 98) for the first six months of life. Vitamin D levels and allergic disease outcomes were followed up. There were no statistically significant differences in incidence of any medically diagnosed allergic disease outcomes or allergen sensitization rates between the vitamin D-supplemented and placebo groups at either 1 year or at 2.5 years of age. In conclusion, for “allergy high-risk” infants who had sufficient vitamin D status at birth, early infancy oral vitamin D supplementation does not appear to reduce the development of early childhood allergic disease.

The dramatic rise in allergic disease has occurred in tandem with recent environmental changes and increasing indoor lifestyle culture. While multifactorial, one consistent allergy risk factor has been reduced sunlight exposure. However, vitamin D supplementation studies have been disappointing in preventing allergy, raising possible independent effects of ultraviolet (UV) light exposure. The aim of this study was to examine whether UV light exposure influences the development of allergic disease in early childhood. Direct sunlight exposure (290–380 nm) in early infancy was measured via UV dosimeters. Outdoor exposure, sun protective behaviours, and allergy outcomes were assessed over the first 2.5 years of life with clinical assessment appointments at 3, 6, 12 and 30 months of age. Children with eczema had less (p = 0.038) direct UV light exposure between 0–3 months of age (median (IQR) 747 (473–1439) J/m²) than children without eczema (median (IQR) 1204 (1717–1843) J/m²); and less outdoor exposure time (7 min/day) between 11 a.m. and 3 p.m. compared to children without eczema (20 min/day, p = 0.011). These associations were seen independent of vitamin D status, and after adjusting for other potential confounders. Whilst we could not find any associations between direct UV light exposure and other allergic disease outcomes, exposure to UV light appears to be beneficial in reducing the risk of eczema development in early childhood. Further research is required to determine optimal levels of UV light exposure while balancing the potential risks.

Asthma is the most common admission diagnosis for children in many developed countries, and exacerbations of asthma symptoms are associated with significant costs for healthcare systems.¹ x 1 Lane, S., Molina, J., and Plusa, T. An international observational prospective study to determine the cost of asthma exacerbations (COAX). Respir Med. 2006; 100: 434–450 Abstract | Full Text | Full Text PDF | PubMed | Scopus (69) | Google Scholar See all References ^{, 2} x 2 Skrepnek, G.H. and Skrepnek, S.V. Epidemiology, clinical and economic burden, and natural history of chronic obstructive pulmonary disease and asthma. Am J Manag Care. 2004; 10: S129–S138 PubMed | Google Scholar See all References Epidemiologic studies have demonstrated that 60%-85% of acute asthma exacerbations are associated with a viral respiratory infection (VRI).³ x 3 Johnston, S.L., Pattemore, P.K., Sanderson, G., Smith, S., Lampe, F., Josephs, L. et al. Community study of role of viral infections in exacerbations of asthma in 9- to 11-year-old children. BMJ. 1995; 310: 1225–1229 Crossref | PubMed | Scopus (1423) | Google Scholar See all References ^{, 4} x 4 Heymann, P.W., Platts-Mills, T.A., and Johnston, S.L. Role of viral infections, atopy and antiviral immunity in the etiology of wheezing exacerbations among children and young adults. Pediatr Infect Dis J. 2005; 24: S217–S222 Crossref | PubMed | Scopus (68) | Google Scholar See all References Approximately two-thirds of these infections are due to rhinovirus (RV), but other respiratory viruses have been identified as well.⁵ x 5 Corne, J.M., Marshall, C., Smith, S., Schreiber, J., Sanderson, G., Holgate, S.T. et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet. 2002; 359: 831–834 Abstract | Full Text | Full Text PDF | PubMed | Scopus (389) | Google Scholar See all References Respiratory viruses have been associated with airway inflammation and narrowing, with resulting reduced lung function in children.³ x 3 Johnston, S.L., Pattemore, P.K., Sanderson, G., Smith, S., Lampe, F., Josephs, L. et al. Community study of role of viral infections in exacerbations of asthma in 9- to 11-year-old children. BMJ. 1995; 310: 1225–1229 Crossref | PubMed | Scopus (1423) | Google Scholar See all References ^{, 7} x 7 Papadopoulos, N.G., Xepapadaki, P., Mallia, P., Brusselle, G., Watelet, J.B., Xatzipsalti, M. et al. Mechanisms of virus-induced asthma exacerbations: state of the art. A GA2LEN and InterAirways document. Allergy. 2007; 62: 457–470 Crossref | PubMed | Scopus (92) | Google Scholar See all References Respiratory viruses also may act synergistically with other factors associated with asthma, particularly sensitization and exposure to allergens.⁶ x 6 Murray, C.S., Poletti, G., Kebadze, T., Morris, J., Woodcock, A., Johnston, S.L. et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax. 2006; 61: 376–382 Crossref | PubMed | Scopus (314) | Google Scholar See all References However, whereas the mechanisms of virus-induced asthma exacerbations have been studied intensively using in vitro and in vivo experimental models,⁷ x 7 Papadopoulos, N.G., Xepapadaki, P., Mallia, P., Brusselle, G., Watelet, J.B., Xatzipsalti, M. et al. Mechanisms of virus-induced asthma exacerbations: state of the art. A GA2LEN and InterAirways document. Allergy. 2007; 62: 457–470 Crossref | PubMed | Scopus (92) | Google Scholar See all References the possibility that viruses could influence treatment response during an acute exacerbation has not yet been defined.