The Role of Vitamin D in Inflammatory Diseases

Over the last decades, non-skeletal effects of vitamin D3 in several chronic diseases, such as immune-mediated diseases, have gained increasing attention. 1 alpha-hydroxylase (CYP27B1) and vitamin D receptor (VDR) have been found to be expressed by different cell types of the immune system. These cells are thus able to convert 25-(OH)-vitamin D3 to 1,25-(OH) 2-vitamin D3, which act locally in an autocrine fashion, without being subject to control by the endocrine system. Consequently, different immunomodulating effects can be exerted through vitamin D3 including strengthening of the innate immune response, with an amplification of antibacterial effects, and also different regulatory effects of the adaptive immune response. A lack of vitamin D is regarded to be associated with the development of different autoimmune diseases such as type I diabetes mellitus, multiple sclerosis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This is of importance considering the growing evidence of an insufficient alimentary supply of vitamin D world-wide. Low and even very low 25-(OH)-vitamin D3 levels can be found in almost all rheumatic diseases including RA, SLE, systemic sclerosis, ankylosing spondylitis and Behcet's disease. In all of these diseases an inverse correlation between 25-(OH)-vitamin D3 levels and disease activity can be found. Until now, the underlying cause of this inverse correlation is unclear. Whether high disease activity induces low 25-(OH)-vitamin D3 levels or vice versa remains to be clarified. So far it is not proven that an insufficient supply of vitamin D increases the incidence of RA or SLE. However, considering the immunomodulatory effects of vitamin D on the cells of the immune system, the use of vitamin D3 as a combination partner in the immunosuppressive treatment of autoimmune diseases would be conceivable. Yet, the results of some open-label studies and few randomised controlled trials (RCT) have not revealed any convincing effect so far. Nevertheless, it cannot be excluded that the vitamin D3 dosages and the duration of the trials, both of which were based on the endocrine effects of vitamin D3, were insufficient to achieve autocrine immunomodulatory efficacy. In order to answer this question further RCT are required which use dosages adjusted to individual 25-(OH)-vitamin D3 serum levels, achieve higher systemic levels of 25-(OH)-Vitamin D3 and are of longer duration.