title: 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 II(hi) 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.
authors: Arthritis Research Laboratory, Hanson Institute, SA Pathology, Adelaide, South Australia, Australia.
authors: Mahin
authors: M
authors: Moghaddami
authors: Graham
authors: G
authors: Mayrhofer
authors: Paul H
authors: PH
authors: Anderson
authors: Howard A
authors: HA
authors: Morris
authors: Mark
authors: M
authors: Van Der Hoek
authors: Leslie G
authors: LG
authors: Cleland
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D013583:Synovial Membrane / Q000737:chemistry / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014807:Vitamin D / Q000008:administration & dosage / Q000494:pharmacology*; D014808:Vitamin D Deficiency / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D014807:Vitamin D; D017493:Leukocyte Common Antigens