Association between vitamin D, antimicrobial peptides and urinary tract infection in infants and young children.

AIM: Vitamin D stimulates production of the endogenous antimicrobial peptides cathelicidin and ß-defensin-2, which are expressed in the urinary tract. We investigated vitamin D status and levels of cathelicidin and ß-defensin-2 and their association with urinary tract infection (UTI). METHODS: The study included 120 children under three years of age: 76 children with UTIs and 44 otherwise healthy children with congenital hydronephrosis. Serum 25-hydroxycholecalciferol levels were measured by direct competitive electro-chemiluminescence immunoassay, and plasma cathelicidin and ß-defensin-2 concentrations were analysed by enzyme-linked immunosorbent assay. RESULTS: We found that vitamin D insufficiency and deficiency are prevalent in young children (21%). Serum vitamin D levels negatively correlated with age and were significantly lower in girls. Levels of vitamin D positively correlated with levels of cathelicidin but not with ß-defensin-2. Low concentrations of vitamin D were associated with UTIs in girls, but we did not see any correlation with the recurrence of infection at one-year follow-up. CONCLUSION: Vitamin D deficiency is common and may prove to be a risk factor for UTIs especially in girls. We hypothesise that adequate supplementation with vitamin D may become a way to prevent first-time UTIs.

Prenatal vitamin D3 supplementation suppresses LL-37 peptide expression in ex vivo activated neonatal macrophages but not their killing capacity.

Vitamin D has regulatory effects on innate immunity. In the present study, we aimed to assess the effect of prenatal vitamin D3 (vitD3) supplementation on neonatal innate immunity in a randomised, placebo-controlled trial by evaluating cathelicidin (LL-37) expression and the killing capacity of macrophages. Healthy pregnant women (n 129) attending a clinic in Dhaka were randomised to receive either a weekly oral dose of 0·875 mg vitD3 or placebo starting from 26 weeks of gestation up to delivery. Serum, plasma and monocyte-derived macrophages (MDM) were obtained from the cord blood. 25-Hydroxyvitamin D (25(OH)D) concentration was measured in serum. MDM were stimulated with or without Toll-like-receptor 4 ligand (TLR4L). Innate immune function was assessed by measuring LL-37 peptide levels in the culture supernatant of MDM by ELISA, LL-37 transcript levels by quantitative PCR, and ex vivo bactericidal capacity of MDM. VitD3 supplementation did not increase LL-37 peptide levels in plasma or in the extracellular fluid of macrophages with or without TLR4L induction. However, stimulated intracellular LL-37 expression (ratio of stimulated:unstimulated MDM) was significantly reduced in the vitamin D group v. placebo (P=0·02). Multivariate-adjusted analyses showed that intracellular LL-37 peptide concentration from stimulated MDM was inversely associated with 25(OH)D concentration in serum (P=0·03). TLR4L stimulation increased the bactericidal capacity of MDM compared with the unstimulated ones (P=0·01); however, there was no difference in killing capacity between the two groups. A weekly dose of 0·875 mg vitD3 to healthy pregnant women suppressed the intracellular LL-37 peptide stores of activated macrophages, but did not significantly affect the ex vivo bactericidal capacity of cord blood MDM.

Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation.

Patients with cystic fibrosis (CF) suffer from chronic lung infection and inflammation leading to respiratory failure. Vitamin D deficiency is common in patients with CF, and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF. We conducted a double-blinded, placebo-controlled, randomized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation. We randomized 30 adults with CF hospitalized with a pulmonary exacerbation to 250,000 IU of cholecalciferol or placebo, and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention. In the vitamin D group, there was a 50.4% reduction in tumor necrosis factor-α (TNF-α) at 12 weeks (P<0.01), and there was a trend for a 64.5% reduction in interleukin-6 (IL-6) (P=0.09). There were no significant changes in IL-1ß, IL-8, IL-10, IL-18BP and NGAL (neutrophil gelatinase-associated lipocalin). We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines, IL-6 and TNF-α. This study supports the concept that vitamin D may help regulate inflammation in CF, and that further research is needed to elucidate the potential mechanisms involved and the impact on clinical outcomes.