Maternal vitamin D and E intakes during early pregnancy are associated with airway epithelial cell responses in neonates.

BACKGROUND: Antenatal factors including maternal diet may predispose to airway disease, possibly by impacting on fetal airway development. OBJECTIVE: This cohort study tested the hypothesis that maternal vitamin D and E status in early pregnancy is associated with airway epithelial cell (AEC) responses in new born infants and examined constitutive and TNFα/IL-1ß, house dust mite (HDM) extract or lipopolysaccharide (LPS)-stimulated neonatal AEC responses in vitro. METHODS: Maternal dietary vitamin D and E intakes (plasma 25[OH]D3 or α-tocopherol) were characterized at 10-12 weeks gestation. Neonatal nasal AECs were collected soon after birth and cultured to tertiary passage. Constitutive and stimulated - TNFα/IL-1ß, HDM extract or LPS - secretory responses (VEGF, RANTES, MCP-1, IL-17A, IFN-γ, GM-CSF, eotaxin, MIP1-α, MIP1-ß, ICAM, IL-6, IL-8, IL-10, TNF) in 139 AEC cultures were quantified. RESULTS: AEC mediator release was greater following TNF-α/IL-1ß, HDM or LPS stimulation compared to constitutive release. Increased maternal dietary vitamin D was associated with significant increases in IL-10 release by AEC after stimulation with TNF-α/IL-1ß (P = 0.024) or HDM (P = 0.049). Maternal plasma α-tocopherol at 10-12 weeks gestation was positively associated with MIP1α (Spearman's rho 0.242, P = 0.009) and IL-3 (ρ 0.189, P = 0.043) responses after TNF-α/IL-1ß stimulation and negatively associated with TNF (ρ -0.404, P = 0.011) and MIP1ß (ρ -0.322, P = 0.046) responses after LPS stimulation. DISCUSSION: Neonatal AECs respond to pro-inflammatory and allergenic stimuli in vitro demonstrating their potential to function as components of the innate immune response. Our findings suggest that associations exist between maternal micronutrient intake during early pregnancy and aspects of stimulated neonatal airway epithelial cell secretory function that may in turn impact on the development of asthma and/or allergic rhinitis in later life.

Inhibitory effects of Montelukast on mediator release by nasal epithelial cells from asthmatic subjects with or without allergic rhinitis.

AIMS: This study tested inhibitory effects of in vitro Montelukast treatment on nasal airway epithelial cells (AEC) cultured from asthmatic patients treated with Montelukast with and without concomitant allergic rhinitis. We further examined the effect of Montelukast withdrawal in these patients on cytokine release from cultured nasal AEC. METHODS: Nasal AEC were collected by brushings from subjects with a history of stable (no exacerbations or change in medication for ≥ 1 month) physician confirmed mild/moderate asthma whose asthma symptoms were documented to benefit from Montelukast treatment (NCT01230437). Release of the following mediators by nasal AEC were measured: IL-8, IL-6, IL-10, GM-CSF, RANTES, eotaxin and IFN-γ. Nasal AEC were cultured before and one week after withdrawal of their Montelukast treatment. RESULTS: Forty two asthmatics were recruited. Nasal AEC were successfully cultured in 17 at the first assessment, 14 at the second assessment and in 10 individuals at both assessments. Nasal AEC release was no different between asthmatics with or without allergic rhinitis. Montelukast significantly suppressed the release of IL-8 (p = 0.016), IL-6 (p = 0.006), RANTES (p = 0.002) and IFN-γ (p = 0.046), in a dose dependent manner in unstimulated cultures but not in those stimulated with IL-1/TNF. Withdrawal of Montelukast treatment, was associated with increased IL-8 and RANTES secretion in unstimulated nasal AEC cultured from subjects with asthma and allergic rhinitis but not with asthma alone. CONCLUSIONS: Montelukast treatment for asthma symptoms reversibly suppresses nasal AEC release of pro-inflammatory mediators (i.e. IL-8 and RANTES) but only in those cells cultured from subjects with concomitant allergic rhinitis.