title: Reversible control by vitamin D of granulocytes and bacteria in the lungs of mice: an ovalbumin-induced model of allergic airway disease.
abstract: Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a 'low dose' model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.
authors.affiliation: Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia. shelleyg@ichr.uwa.edu.au
authors.forename: Shelley
authors.initials: S
authors.lastname: Gorman
authors.forename: Clare E
authors.initials: CE
authors.lastname: Weeden
authors.forename: Daryl H W
authors.initials: DH
authors.lastname: Tan
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Scott
authors.forename: Julie
authors.initials: J
authors.lastname: Hart
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Foong
authors.forename: Danny
authors.initials: D
authors.lastname: Mok
authors.forename: Nahiid
authors.initials: N
authors.lastname: Stephens
authors.forename: Graeme
authors.initials: G
authors.lastname: Zosky
authors.forename: Prue H
authors.initials: PH
authors.lastname: Hart
mesh_terms: D000336:Aerosols; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology; D001419:Bacteria / Q000187:drug effects*; D058491:Bacterial Load / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology* / Q000503:physiopathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014807:Vitamin D / Q000494:pharmacology*; D014808:Vitamin D Deficiency / Q000150:complications / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology
chemical_list: D000336:Aerosols; D000485:Allergens; D007074:Immunoglobulin G; D012333:RNA, Messenger; D014807:Vitamin D; D007073:Immunoglobulin E; D010047:Ovalbumin