Efficacy and mechanisms of action of vitamin D in experimental polyarthritis

Abstract

Vitamin D (vit D) status has been linked to the occurrence and severity of auto-immune and inflammatory diseases. This study evaluates the effects of vit D status on adoptive transfer of adjuvant-induced arthritis (ATA). Rats maintained on diets replete or deficient in vit D3 received arthritogenic thoracic duct cells and were monitored for severity of arthritis. CD45+ cells obtained by collagenase digestion of hind-paw synovium-rich tissues (SRTs) were analysed to observe the effects of dietary vit D3 on the inflammatory process. Arthritis was more severe in vitamin D-deficient (vit-D−) rats compared with vitamin D-replete (vit-D+) rats. Resolution was delayed in vit-D− rats compared with vit-D+ rats, or rats fed standard chow. During the acute phase of ATA, numbers of CD45+ cells were significantly increased in the SRTs of vit-D− rats compared with vit-D+ rats. This increase involved T-cells, polymorphonuclear leukocytes, macrophages, dendritic cells (DCs) and MHC IIhi cells that resemble activated monocytes. A major difference between the dietary groups was that most DCs at the peak of inflammation in vit-D− rats were CD4–, whereas in convalescent vit-D+ rats most expressed CD4. Multiple categories of genes expressed by DCs differed between deficient and replete rats, with deficiency being associated with relative upregulation of certain pro-inflammatory genes and replete status being associated with upregulation of genes associated with resolution of inflammation. The findings indicate that ATA is more severe and prolonged in vit-D deficiency, that vit-D deficiency promotes accumulation of CD4− DCs in synovium during ATA and that a gene-expression profile is likely to contribute to the observed increased severity and duration of arthritis.