Vitamin D Deficiency Has Protective Effects In A Mouse Model Of Chronic House Dust Mite Exposure

Rationale: Reduced levels of vitamin D are associated with airway hyperresponsiveness (AHR) and increased markers of asthma severity. We hypothesized that vitamin D deficiency exacerbates respiratory outcomes in asthma and aimed to determine whether vitamin D deficiency would increase AHR and inflammation in a mouse model of chronic allergic asthma.

Methods: A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D-deficient or -replete diets. Offspring from -deficient and -replete mice of both sexes at 8 weeks of age were intranasally inoculated with house dust mite (HDM) extract (25 g of protein in 50 L of saline) or saline as a control 5 days a week for 5 weeks. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine 72 hours after the last HDM exposure. Bronchoalveolar lavage (BAL) fluid was collected to assess cellular inflammation and cytokine levels.

Results: Chronic HDM exposure increased baseline airway resistance in female vitamin D-replete mice compared with vitamin D-deficient mice (p<0.05) (Figure 1). Similarly, HDM exposure increased the maximum response in tissue elastance to methacholine in vitamin D-replete male mice compared to deficient male mice (p<0.05). HDM exposed vitamin D-deficient female mice however demonstrated increased sensitivity to methacholine, requiring a significantly lower concentration of methacholine to elicit a doubling in airway resistance (EC )(p<0.05) (Figure 2). Total cell and eosinophil counts were 200 significantly increased in the BAL fluid of mice chronically exposed to HDM, however there was no effect of vitamin D deficiency. Transforming growth factor (TGF)- levels were higher in the BAL fluid of chronic HDM exposed vitamin D-replete female mice compared with deficient mice (p<0.05).

Conclusions: Vitamin D deficiency causes increased sensitivity to methacholine in HDM exposed female mice but overall does not have an effect on cellular inflammation and protects mice against physiological impairments induced by chronic HDM exposure.