Vitamin D Deficiency and Rheumatoid Arthritis

Abstract

Vitamin D (VitD) is a hormone primarily synthesized in human skin under the stimulation of ultraviolet radiation. Beyond its endocrine role in bone metabolism, VitD is endowed with remarkable immunomodulatory properties. The effects of VitD on the immune system include the enhancement of microbicidal ability of monocytes/macrophages and the down-modulation of inflammatory cytokines produced by T lymphocytes. VitD deficiency is involved in many health problems, including immune-mediated diseases such as autoimmune disorders. Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease that compromises the joints, causing cartilage destruction and bone erosion. RA treatment usually consists of combined therapies that generally suppress the entire immune response leading to increased susceptibility to infections. This review describes the main effects of VitD on innate and adaptive immune system and also VitD status in inflammatory rheumatic diseases such as RA. Despite some controversies, the majority of reports reinforce the idea that lower VitD levels correlate with more severe clinical manifestations in RA and other rheumatic diseases. Therefore, supplementation with VitD to achieve normal serum levels is worthwhile as an aforethought. Original data concerning the potential applicability of 1,25-dihydroxyvitamin D (VitD3), the active form of vitamin D, as a tolerogenic adjuvant are also included. In this sense, the effect of VitD3 associated with proteoglycan (PG), which is a specific cartilage antigen, was tested in the course of experimental arthritis. This association significantly lowered clinical scores and local histopathological alterations. Even though local analysis of T cell subsets and cytokine production did not reveal any difference between the experimental groups, VitD3+PG association significantly reduced cytokine production by spleen cells. These results suggest that VitD3 played a role as a tolerogenic adjuvant by down-modulating the course of experimental RA. Considering this tolerogenic effect of VitD3+PG association, further investigations will reveal its plausible use in human RA.

Micro-CT imaging analysis for the effects of ibandronate and eldecalcitol on secondary osteoporosis and arthritis in adjuvant-induced arthritis rats

“…In the present study, we demonstrated that IBN and/ or ELD increased BMD of trabecular bone in both the lumbar vertebrae and femur and improved several microstructural parameters (BV/TV, SMI, Tb.N, and Tb.Sp) of the trabecular bone in the distal femur. There was an additive effect of combination treatment IBN + ELD compared with single treatments for most trabecular parameters, including cancellous BMD (proximal and distal femur) and bone duced cytokine production by spleen cells in AIA rats (18). In contrast, Oelzner et al reported that vitamin D did not affect inflammation and joint destruction in AIA rats (31).…”

Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis

“…The biological mechanism for seasonal variation in RA activity remains to be elucidated. Vitamin D metabolism might be a contributing factor [47–49], given that vitamin D has effects on innate and acquired immunity [47] and exposure to sunlight is required for ultraviolet B-induced synthesis of vitamin D in the skin. Ishikawa et al demonstrated that serum vitamin D levels follow a lagged pattern relative to the astronomical seasons, peaking in late summer (August) and troughing in late winter (February) [47], possibly as a result of fewer daylight hours and less outdoor activity because of cool or cold weather.…”

Systemic vitamin intake impacting tissue proteomes

“…Deficiency in vitamin D impairs bone mineralization causing rickets in infants/children and osteomalacia in adults [ 174 ]. Vitamin D deficiency is also linked to cardiovascular diseases [ 175 , 176 ], cancer [ 177 , 178 ], neurological impairments [ 179 , 180 ] and autoimmune diseases [ 181 , 182 ]; though underlying mechanisms are not completely understood.…”