Serum 25-hydroxyvitamin D concentrations are associated with nuclear factor kappa-B activity but not with inflammatory markers in healthy normoglycemic adults. Issue 177 (March 2018) - Mousa, Aya
Highlights: This was the first study examining 25-hydroxyvitamin D (25(OH)D) and nuclear factor kappa-B (NFκB) activity in vivo in humans. In healthy adults, 25(OH)D concentrations were positively associated with NFκB activity, but not with pro- or anti-inflammatory markers. Associations with NFκB activity persisted after adjustment for potential confounders, and in a subgroup of vitamin D- deficient participants. Experimental reports of a purely inhibitory effect of vitamin D on NFκB may be underestimating the complex role of vitamin D in immunoregulation. Abstract: Vitamin D has been reported to have anti-inflammatory properties in in vitro and animal studies, which are thought to occur via inhibition of the nuclear factor kappa- B (NFκB) pathway. However, the association between vitamin D and in vivo NFκB activity in humans has not previously been reported. The aim of the present study was to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and NFκB activity in peripheral blood mononuclear cells (PBMCs) as well as plasma inflammatory markers in healthy individuals. We hypothesized that 25(OH)D concentrations would be negatively associated with NFκB activity and pro-inflammatory markers downstream of NFκB, and positively associated with anti-inflammatory markers. We measured circulating 25(OH)D (chemiluminescent immunoassay); anthropometry: body mass index (BMI), waist-to-hip ratio (WHR), and % body fat (dual X-ray absorptiometry); plasma pro- and anti-inflammatory markers: high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and IL-10 (ELISA); and NFκB activity in PBMCs (DNA-binding assay). Forty-nine participants were included in the study (21M/28F; age = 31.6 ± 10.2 years (mean ± SD); BMI = 28.4 ± 4.6 kg/m 2 ; % body fat = 30.2 ± 9.3%). Mean 25(OH)D concentration was 48.2 ± 24.5 nmol/l. There were no differences in 25(OH)D concentrations between genders and no association between 25(OH)D concentrations and age, BMI, or % body fat (all p > 0.1). Serum 25(OH)D concentrations were positively associated with NFκB activity in PBMCs (r = 0.48, p = 0.0008) but not with any of the pro- or anti-inflammatory markers measured (all p > 0.1). After adjusting for age, sex, and % body fat, 25(OH)D concentrations remained positively associated with NFκB activity in PBMCs (β = 0.55, p < 0.0001). Although in-vitro studies suggest that vitamin D inhibits NFκB activity, our novel cross-sectional data from a cohort of healthy individuals suggest that vitamin D may regulate rather than inhibit the NFκB pathway. Large-scale intervention and mechanistic studies are needed to further investigate the effects of vitamin D on NFκB activity in vivo in humans.