Local nebulization of 1α,25(OH)2D3 attenuates LPS-induced acute lung inflammation

Background Evidence supports a critical role of vitamin D status on exacerbation in chronic obstructive pulmonary disease, indicating the need to avoid vitamin D deficiency in these patients. However, oral vitamin D supplementation is limited by the potential risk for hypercalcemia. In this study, we investigated if local delivery of vitamin D to the lungs improves vitamin D-mediated anti-inflammatory action in response to acute inflammation without inducing hypercalcemia. Methods We studied vitamin D sufficient (VDS) or deficient (VDD) mice in whom 1 alpha,25(OH)(2)D-3 (0.2 mu g/kg) or a vehicle followed by lipopolysaccharide (LPS 25 mu g) were delivered to the lung as a micro-spray. Results Local 1 alpha,25(OH)(2)D-3 reduced LPS-induced inflammatory cells in bronchoalveolar lavage (BAL) in VDS (absolute number of cells: - 57% and neutrophils - 51% p < 0.01) and tended to diminish LPS-increased CXCL5 BAL levels in VDS (- 40%, p = 0.05) while it had no effect on CXCL1 and CXCL2 in BAL and mRNA in lung of VDS and VDD. It also significantly attenuated the increased IL-13 in BAL and lung, especially in VDD mice (- 41 and - 75%, respectively). mRNA expression of Claudin-18 in lung was significantly lower in VDS mice with local 1 alpha,25(OH)(2)D-3 while Claudin-3, -5 and -8 mRNA levels remained unchanged. Finally, in VDD mice only, LPS reduced lung mRNA expression of adhesion junction Zona-occludens-1, in addition to increasing uric acid and total protein in BAL, which both were prevented by local 1 alpha,25(OH)(2)D-3. Conclusion Under normal levels of vitamin D, local 1 alpha,25(OH)(2)D-3 nebulization into the lung efficiently reduced LPS induction of inflammatory cells in BAL and slightly attenuated LPS-increase in CXCL5. In case of severe vitamin D deficiency, although local 1 alpha,25(OH)(2)D-3 nebulization failed to significantly minimize cellular inflammation in BAL at this dose, it prevented epithelial barrier leakage and damage in lung. Additional research is needed to determine the potential long-term beneficial effects of local 1 alpha,25(OH)2D3 nebulization on lung inflammation.

Automated summary

Local delivery of vitamin D to the lungs efficiently reduced inflammatory cells induced by LPS in bronchoalveolar lavage and slightly attenuated an increase in CXCL5. In cases of severe vitamin D deficiency, despite not significantly minimizing cellular inflammation, local vitamin D prevented epithelial barrier leakage and damage in the lung. Additional research is needed to determine the long-term beneficial effects of local vitamin D delivery on lung inflammation.