Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

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.     

Development of the γ-Aminobutyric Acid Neurotransmitter System in the Rat Cerebral Cortex During Repeated Administration of the GABA-Transaminase Inhibitor Ethanolamine O-Sulphate

Ethanolamine O-sulphate (400 mg/kg, i.p.) was administered to rat pups at 9 days of age and on alternate days up to 17 days of age. At 18 days of age, gamma-aminobutyric acid (GABA) concentration was increased (three- to fourfold), glutamic acid decarboxylase (GAD) activity reduced to 55% of control, and the number of GABAA and GABAB binding sites increased in the cerebral cortex. This is the same pattern of change as seen previously with oral administration of ethanolamine O-sulphate to the adult rat but the changes occur more rapidly in the developing rat. A lower dose of ethanolamine O-sulphate (100 mg/kg, i.p.), administered according to the same schedule, caused a twofold increase in cortical GABA at 18 days of age whereas GAD activity and GABAA binding were not significantly altered.