927 Oral vitamin D rapidly attenuates inflammation from sunburn: An interventional study

      Although diverse immunomodulatory effects of vitamin D are increasingly being recognized, the ability of oral vitamin D to rapidly modulate immune responses in vivo has not been established in humans. We designed an interventional study to test the hypothesis that oral vitamin D would be capable of rapidly attenuating experimental sunburn. Twenty healthy adults were randomized, in a double-blinded fashion, to receive either placebo or a high dose of vitamin D3 (cholecalciferol) one hour after experimental sunburn induced by an erythemogenic dose of simulated solar radiation. As compared to placebo, participants receiving vitamin D3 (200,000 IU) demonstrated reduced expression of the pro-inflammatory mediators TNF-α (p=0.04) and iNOS (p=0.02) in skin biopsy specimens 48 hours after experimental sunburn. A blinded unsupervised hierarchical clustering of participants based on global gene expression profiles revealed that participants with significantly higher serum vitamin D3 levels after treatment (p=0.007) demonstrated increased skin expression of the anti-inflammatory mediator arginase-1 (p=0.005), a sustained reduction in skin redness (p=0.02), and significant expression of skin barrier repair genes. In contrast, participants with lower serum vitamin D3 levels had significant expression of pro-inflammatory genes. These findings demonstrate that oral vitamin D is capable of rapidly attenuating experimental sunburn, and implicate arginase-1 up-regulation as a novel mechanism by which vitamin D exerts anti-inflammatory effects in humans. These results have broad implications for the role of vitamin D in skin homeostasis, and suggest that oral vitamin D may be clinically therapeutic for its immunomodulatory properties.