25-hydroxyvitamin D promotes the long-term effects of specific immunotherapy (SIT) in allergic airway inflammation in mice

Introduction: Vitamin D mediates immune functions and Vitamin D deficiency has been associated with exacerbations and elevated serum IgE levels in asthma patients. The active vitamin D metabolite calcitriol suppresses allergen-specific IgE production in B lymphocytes, which are capable to synthesize calcitriol from its precursor 25-hydroxyvitamin D (25(OH)D). As vitamin D deficiency is frequently observed during the UV-deprived winter months, we determined the impact of 25(OH)D given together with SIT in a model of murine immunotherapy. Methods: 25(OH)D-deficient mice were sensitized with ovalbumin (OVA) and treated with SIT with or without adjuvant 25(OH)D application. After 5 weeks, an OVA recall was performed and mice were challenged with aerosolized OVA on 3 consecutive days and, two days later, airway hyperresponsiveness (AHR) was assessed in isolated perfused and ventilated lungs. Serum immunoglobulins, bronchoalveolar lavage fluid (BALF) leukocyte differentials and BALF cytokines were quantified. Results: OVA sensitization and challenge resulted in specific IgE induction, allergic airway inflammation and AHR compared to nonsensitized controls. SIT compared to sensitized controls without SIT led to reduced induction of serum immunoglobulins and pulmonary leukocyte influx, whereas BALF cytokine levels and AHR were comparable. Adjuvant 25(OH)D along with SIT led to diminished AHR compared to SIT alone and reduced BALF Th2 cytokine levels compared to sensitized controls without SIT. Conclusion: Adjuvant 25(OH)D may improve long-term efficacy of allergen-specific immunotherapy in allergic asthma patients.