Introduction There is convincing evidence of the clinical health benefits of adequate vitamin D in many respiratory diseases but the evidence in cystic fibrosis (CF) is unclear. There are increasing data on the role of vitamin D as an immunomodulatory agent and it is thought, from in-vitro data, that this may be via induction of the antimicrobial peptides, LL37 and HβD-2. We hypothesised that antimicrobial peptide levels would be increased in children with adequate vitamin D and this could account for reported improvements in lung function via improved airway defence.
Aims and methods The main aim was to establish if a relationship exists between vitamin D and antimicrobial peptides, LL37 and HβD-2, and whether any clinically beneficial effects of adequate vitamin D exist in children with CF. Bronchoalveolar fluid (BALF) supernatant levels of LL37 and HβD-2 were by measured by ELISA and serum 25(OH)D2 by mass spectrometry coupled with high-performance liquid chromatography.
Results Samples were collected from 120 children with CF (58% female); median age (range) 6.9 (0.1–17.6) years. One third of patients were vitamin D insufficient (<50 nmol/L). Median 25(OH)D2 was 57 nmol/L (range 7–191 nmol/L). LL37 ranged from 0.1–21.9 ng/mL with median value of 0.49 ng/mL and HβD-2 from <15.6 - >1000 pg/ml, median 150 pg/ml.
LL37 was significantly correlated with serum neutrophils (r= 0.4, P<0.0001), BALF total cell count (r=0.7, p<0.0001), and BALF neutrophil differential (r= 0.5, p<0.0001). These relationships were not seen with HβD-2. Contrary to our hypothesis neither LL37 nor HβD-2 correlated with vitamin D and no differences were seen between vitamin D ‘adequate’ and ‘insufficient’ patients. There was no association seen between vitamin D and FEV1 (r2=0.01, p=0.4).
Conclusions Our results demonstrate that there is not a relationship between serum 25(OH)D2 and BALF HβD-2 or LL37. If vitamin D is involved in the induction of such defence peptides in-vivo, the impact of this on protein levels may be limited in the degradative environment of the inflamed airway. In addition, we found no clinical or physiological effects of vitamin D deficiency. If any beneficial effect of vitamin D on respiratory health does exist in CF, it is small and not mediated via the antimicrobial pathway.
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