Low vitamin D status is associated with inflammatory response in older patients with cerebral small vessel disease

Objectives: This study aimed to determine the association of the NF-KB inflammatory signaling pathway with vitamin D status in older cerebral small vessel disease (SVD) patients.Methods: We measured serum 25(OH)D, pro-and anti-inflammatory cytokines, and mRNA levels of the vitamin D -activating enzyme, CYP27B1, as well as NF-kB, COX-2, the chemokine-CCL2, IL-1 beta, IL-6, TNF-alpha, TGF-beta, and IL-10, in cerebral SVD patients aged >= 60 years presenting with vascular dementia and age and gender-matched healthy controls.Results: Low vitamin D status (insufficiency: serum 25(OH)D 12-20 ng/ml; deficiency: <= 12 ng/ml) was more prevalent among patients compared to controls. The mRNA levels of NF-kB, COX-2, CCL2, IL-1 beta, and IL-6, and serum levels of pro-inflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha) were significantly higher in cases compared to controls. There was a significant correlation between CYP27B1 and NF-kB, COX-2, CCL2, and IL-1 beta gene expression. Serum IL-1 alpha, IL-1 beta, and IL-6 concentrations and the expression of CCL-2, NF-kB2, and NF-kB3 genes were higher in vitamin D-deficient subjects compared to vitamin D-sufficient subjects. There was a sig-nificant negative correlation between serum 25(OH)D and IL-1 alpha, IL-6, and TNF-alpha, and a positive correlation between 25(OH)D and IL-10.Conclusion: Low vitamin D is associated with an inflammatory response via NF-kB signaling, which could play a role in the etio-pathogenesis of SVD. Further large-scale studies are required to validate our findings.