Influence of Vitamin D Metabolites on Plasma Cytokine Concentrations in Endurance Sport Athletes and on Multiantigen Stimulated Cytokine Production by Whole Blood and Peripheral Blood Mononuclear Cell Cultures

Aim. Our aims were to determine the influence of plasma total 25-hydroxy vitamin D (25(OH)D) status on the plasma cytokine concentrations in athletes and the in vitro effects of different doses of 1, 25 dihydroxyvitamin D3 (1, 25(OH)2D3) on multiantigen stimulated cytokine production by whole blood and peripheral blood mononuclear cell (PBMC) cultures. Methods. Plasma samples from 43 athletes with high and low levels of 25(OH)D were assayed for the concentrations of cytokines. The whole blood samples and PBMCs from healthy subjects were incubated in vitro with a multi-antigen vaccine and different doses of added 1, 25(OH)2D3. The circulating cytokines and stimulated whole blood and PBMC culture production of cytokines were determined using a biochip assay. Results. The circulating interleukin-(IL-)10 and interferon-(IFN-) concentrations were significantly higher in the vitamin D sufficient athletes. Furthermore, the production of tumour necrosis factor-(TNF-) , IL-6, IFN- , IL-2, and IL-10 by whole blood culture was significantly inhibited by 1, 25(OH)2D3 concentrations of 1000？pmol/L or 10000？pmol/L. Conclusions. We found that the influence of vitamin D on circulating cytokines might be different in athletes compared with nonathletes and cytokines production by whole blood culture was not influenced by 1, 25(OH)2D3 in concentrations within the normal healthy range. 1. Introduction Vitamin D can be obtained either from dietary sources or the epidermal layer of the skin via exposure to sunlight. The endogenously synthesised vitamin D3 and diet-derived D2 and D3 are hydroxylated in the liver to form 25(OH)D. 25(OH)D is the main storage form, which can be stored in muscles and adipose tissue, and is the major circulating metabolite of vitamin D, with a plasma half-life of 2-3 weeks. Therefore, the plasma concentration of 25(OH)D is considered to be the primary indicator of vitamin D status [1]. Plasma 25(OH)D values commonly accepted as the reference range [2] are as follows. In healthy humans, 25(OH)D > 100？nmol/L are defined as optimal vitamin D status and levels from 50 to 100？nmol/L are defined as adequate. Plasma levels of 25(OH)D < 50？nmol/L are proposed to define inadequate vitamin D status and values < 30？nmol/L represent vitamin D deficiency. Subsequently, 25(OH)D can be converted in the kidney to the biologically active form, 1, 25(OH)2D, by 1- -hydroxylase, an enzyme which is stimulated by parathyroid hormone when serum calcium and phosphate concentrations fall below the physiological range. Normal concentrations of circulating 1, 25(OH)2D are