Can vitamin D boost production and circulating cathelicidin levels?

SESSION 3 - VITAMIN D - ORAL COMMUNICATIONIntroduction :The vitamin D deficiency (vitD) is widespread in France, especially in the elderly, causing in addition to osteoskeletal disorders, an increase of the infectious risk. VitD exerts immunomulatory effects after binding to its receptor (VDR) expressed by certain immune cells including peripheral blood mononuclear cells (PBMC). These effects could be explained in part by the ability of vitD to stimulate the production of antimicrobial peptides, such as human cathelicidin, which has vitD response elements in its promoter (VDRE). The aim of this work was to determine whether vitD can induce the expression and production of cathelicidin in circulating immune cells both by i) ex vivo and ii) in vivo approaches.Methods:i) PBMCs collected from healthy donors were incubated ex vivo for 24 h and 48 h in the presence of different doses of vitD (0 ng/ml: control; 25 ng/ml: deficiency; 75 ng/ml: physiological; 125 ng/ml : supraphysiological) and then stimulated or not by a bacterial agent (extract of Escherichia coli Lipopolysaccharides (LPS): 100 ng / ml); or a viral mimetic agent(synthetic double-stranded RNA Poly (I: C) (PIC): 10 μg / ml). ii) Leukocytes and serum from healthy volunteers (> 65 years) were collected after randomization (V1), then 3 months after vitD or placebo supplementation (V2), and then 28 days later after influenza vaccination (V3). Gene expression was assessed by quantitative PCR and protein expression by western blot. Cathelicidin concentrations were determined by ELISA. Results:i) Ex vivo, vitD significantly induced cathelicidin gene expression at t24 h with a maximum effect at 125 ng / ml in either unstimulated (x9) or stimulated LPS (x37) and PIC (x23). This intracellular overexpression is found significantly at the protein level at t48h under unstimulated conditions (x 1.5, D125) and stimulated at LPS (x1.7, D125). The excretion of the peptide in the supernatant is induced significantly by LPS and PIC with a tendency to a dose effect of vitamin D. ii) In vivo, a significant overexpression of cathelicidin is observed in the supplemented vs placebo group at V3 after vaccination (x9.15, p