Association of vitamin D and antimicrobial peptide production during late-phase allergic responses in the lung

Background: Vitamin D may play important roles in regulating immune responses and in defence against infectious diseases by effects on both innate and adaptive immune responses. Little is known regarding activation of vitamin D within airway tissues and its relationship to inflammation and antimicrobial responses. Objective: The objective of this study was to investigate the activation of vitamin D within the airways and to define relationships between vitamin D metabolites and measures of inflammatory and antimicrobial responses assessed by bronchoalveolar lavage (BAL) during late-phase responses following allergen challenge of allergic subjects. Methods: Segmental allergen challenge was performed with saline and allergen in 16 adult allergic subjects. BAL was performed in both saline and allergen-challenged sites 20-24 h. after challenge. Following extraction from BAL fluids, levels of 25-hydroxy-vitamin D (25(OH)D) and 1,25-dihydroxy-vitamin D (1,25(OH) ₂D) were assayed by specific radioimmunoassays. The cleavage product of cathelicidin, LL-37, was assayed by ELISA. Cellular constituents and albumin were measured. Results: Levels of vitamin D metabolites were increased in concentrated BAL fluids after allergen compared to saline challenge. Levels of 1,25(OH) ₂D increased from largely undetectable to 2.5 pm (median; range: 1-29.5; P = 0.005) while 25(OH)D increased from 3.2 (0.8-6.2) to 6.2 (1.5-184.9) nm (P = 0.0006). Levels of LL-37 increased from 2.1 (1.4-4.1) to 14.5 (2.2-106.7) ng/mL BAL (P = 0.0005). Levels of LL-37, 1,25(OH) ₂D, and 25(OH)D following allergen challenge were correlated with each other (P < 0.0001), cellular changes, and levels of albumin (P < 0.001). Conclusions and Clinical Relevance: Levels of vitamin D metabolites, particularly 1,25(OH) ₂D, were low within the airways and increased after allergen challenge. The increases correlated with the magnitude of inflammation and increases in cathelicidin. Normalization to albumin suggested plasma exudation as a mechanism for the increases. The findings support a role for vitamin D in allergic and innate immune responses in the lung.