Oral Presentation 6th Australian Health and Medical Research Congress 2012

‘D’-secting the importance of vitamin D and ultraviolet radiation for the regulation of asthma (#107)

Shelley Gorman 1 , Naomi M Scott 1 , Daryl HW Tan 1 , Clare E Weeden 1 , Robert C Tuckey 2 , Rachel E Fong 1 , Graeme R Zosky 1 , Michele A Grimbaldeston 3 , Prue H Hart 1
  1. Telethon Institute for Child Health Research, Subiaco, WA, Australia
  2. School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, WA, Australia
  3. Division of Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia

The role that sunlight-derived vitamin D has in modulating lung health, particularly in allergic and asthmatic individuals has recently come under intense scrutiny. Our studies have shown that ultraviolet radiation (UVR) suppresses the development of allergic airway disease, the murine model of asthma. There are also latitude gradients for asthma incidence, with greater prevalence for increasing distance from the equator, confirming the potential importance of UVR and UVR-induced mediators like vitamin D in modulating allergic lung disease. Indeed, vitamin D synthesized after UV exposure of the skin may directly suppress allergic disease. Using physiologically-relevant murine models we have scrutinized how vitamin D deficiency or UVR-induced vitamin D modulate the development of allergic airway disease, using the experimental allergen ovalbumin, and T-helper type-2 skewing adjuvant, aluminium hydroxide (alum). The effects of ‘lifetime’ vitamin D deficiency were first examined in BALB/c mice that were maintained on either a vitamin D3-containing or -null diet from conception until adulthood. Vitamin D-replete and -deficient mice had mean serum levels of 25-hydroxyvitamin D (25(OH)D) that were >50 and <20 nmol.L-1, respectively. Enhanced lung inflammation was observed in male but not female vitamin D-deficient mice following intraperitoneal sensitization and boost with OVA (1 µg) and alum (0.2 mg) and subsequent respiratory challenge with OVA. This inflammation was linked with increased bacterial loads in the lungs, and both lung inflammation and bacterial levels were inhibited by subsequent supplementation with dietary vitamin D3. In further studies, following either acute erythemal UVR, or chronic sub-erythemal UVR treatment, serum 25(OH)D levels significantly increased in vitamin D3-deficient female but not male mice. To determine if UVR-induced vitamin D was responsible for suppressing allergic airway disease, responses were measured in mice that were able (female) or unable (male) to synthesize vitamin D after UVR. A single dose of erythemal UVR (8 kJ/m2) suppressed the induction of lung inflammation to a similar degree in female and male mice.  These results suggest that UVR-induced vitamin D does not significantly contribute towards systemic immunosuppression caused by acute erythemal UVR in mice, and highlight the importance of other UVR-immune mediators for modulating the development of allergic diseases like asthma.