M C Liu1, H-Q Xiao, A J Brown, C S Ritter, J Schroeder. 1. Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma & Allergy Center, Baltimore, MD 21224, USA. mcl@jhmi.edu
Abstract
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)(2)D) 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)(2)D 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)(2)D, 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)(2)D, 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.
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)(2)D) 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)(2)D 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)(2)D, 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)(2)D, 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.
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