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The Effect of Vitamin D Supplementation on Mucosal IL-5, MMP9 and Cathelicidin after Nasal Allergen Challenge with Grass Pollen
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Natasha C. Gunawardana, MBBS, MA (Cantab), MRCP, Gaynor Campbell, PhD, Sarah Lindsley, Elizabeth E Mann, Peter J.M. Openshaw, MBBS, PhD, FRCP, Sebastian L. Johnston, MD PhD, Catherine M. Hawrylowicz, Trevor Thomas Hansel, MD PhD
Rationale: Vitamin D may affect the innate and adaptive immune system in allergic disease and there is the need to study effects on the human respiratory mucosa in vivo.

Methods: We carried out a double-blind randomised control study of vitamin D supplementation, using grass pollen nasal allergen challenges (NACs) to assess the effect on mucosal inflammatory mediators. Subjects with a clinical history of hay fever and serum vitamin D (25(OH)D) levels <75nmol/l were recruited; 12 subjects received vitamin D supplementation (4000U orally daily for 28-35 days) and 4 placebo.  NACs were performed before and after supplementation, and nasosorption used to sample mucosal lining fluid (MLF) at hourly intervals to 8h. MLF was eluted by spin filtration, and mediators including IL-5, MMP 9 and cathelicidin levels were measured by sensitive multiplex immunoassay.

Results: Vitamin D supplementation increased serum vitamin D levels (P<0.01). Elevated levels of cathelicidin and MMP9 in nasal MLF were seen between 2-8h after NAC, with IL-5 increasing later at 4-8h. Within the treatment groups there was no significant difference before and after supplementation in induction of IL-5, MMP9 or cathelicidin after NAC (AUC at 0-8h).

Conclusions: Despite normalisation of vitamin D levels, there were no changes in NAC-induced generation of mucosal late phase mediators. In particular, levels of cathelicidin were not significantly altered, even though this is a vitamin D responsive anti-microbial peptide. Cathelicidin and MMP 9 responses were closely related (r=0.74, P<0.0001) and detected earlier than IL-5, possibly reflecting different cell origins.