Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model

Background Asthma is a chronic disease associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodelling. NF-B is a transcriptional factor that regulates and co-ordinates the expression of various inflammatory genes. The NF-B subunits, p50 and Rel-A, are translocated to the nucleus by importin 3 and importin 4. There is growing evidence that vitamin D is a potent immunomodulator. However, the evidence for beneficial or adverse effects of vitamin D in asthma is still unclear. Objective In this study, we examined the effect of vitamin D status on AHR, airway inflammation and cytokines in the bronchoalveolar lavage fluid (BALF) in a murine model of allergic asthma. Methods Female BALB/c mice were fed with special vitamin D-deficient or vitamin D-sufficient (2000IU/kg) or vitamin D-supplemented (10000IU/kg) diet for 13weeks. Mice were sensitized and challenged with ovalbumin (OVA). The effect of vitamin D on lung histology, AHR, T regulatory cells (Tregs) and BALF cytokines was examined. The expression of importin-3 and Rel-A in the lung of OVA-sensitized mice was analysed using immunofluorescence. Results Vitamin D deficiency was associated with higher AHR in OVA-sensitized and challenged mice than those in vitamin D-sufficient mice. This was accompanied with marked signs of airway remodelling, high BALF eosinophilia, increased BALF pro-inflammatory cytokines, reduced BALF IL-10 levels, reduced blood Tregs, increased expression of importin-3 and Rel-A in the lung tissue. Vitamin D supplementation attenuated the pro-inflammatory effects, but did not completely reverse the features of allergic airway inflammation. Conclusion and Clinical Relevance Vitamin D could be beneficial as an adjunct therapy in the treatment of allergic asthma.