Ishikawa Larissa Lumi Watanabe, Colavite Priscila Maria, Fraga-Silva Thais Fernanda de Campos, Mimura Luiza Ayumi Nishiyama, França Thais Graziela Donegá, Zorzella-Pezavento Sofia Fernanda Gonçalves, Chiuso-Minicucci Fernanda, Marcolino Larissa Doddi, Penitenti Marcimara, Ikoma Maura Rosane Valerio, Sartori Alexandrina
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Department of Pathology, Botucatu Medical School, Botucatu, São Paulo, Brazil.
Clin Rev Allergy Immunol. 2017 Jun;52(3):373-388. doi: 10.1007/s12016-016-8577-0.
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.
维生素D（VitD）是一种主要在紫外线辐射刺激下于人体皮肤中合成的激素。除了其在骨代谢中的内分泌作用外，VitD还具有显著的免疫调节特性。VitD对免疫系统的影响包括增强单核细胞/巨噬细胞的杀菌能力以及下调T淋巴细胞产生的炎性细胞因子。VitD缺乏与许多健康问题有关，包括自身免疫性疾病等免疫介导的疾病。类风湿性关节炎（RA）是一种慢性炎症性全身性自身免疫性疾病，会损害关节，导致软骨破坏和骨质侵蚀。RA的治疗通常包括联合疗法，这些疗法通常会抑制整个免疫反应，从而增加感染易感性。本综述描述了VitD对先天性和适应性免疫系统的主要影响以及炎性风湿性疾病（如RA）中的VitD状态。尽管存在一些争议，但大多数报告都强化了这样一种观点，即较低的VitD水平与RA和其他风湿性疾病中更严重的临床表现相关。因此，预先考虑补充VitD以达到正常血清水平是值得的。还包括有关维生素D的活性形式1,25 - 二羟基维生素D（VitD3）作为耐受性佐剂的潜在适用性的原始数据。从这个意义上说，在实验性关节炎过程中测试了VitD3与蛋白聚糖（PG，一种特定的软骨抗原）结合的效果。这种结合显著降低了临床评分和局部组织病理学改变。尽管对T细胞亚群和细胞因子产生的局部分析未显示实验组之间有任何差异，但VitD3 + PG结合显著降低了脾细胞的细胞因子产生。这些结果表明，VitD3通过下调实验性RA的病程起到了耐受性佐剂的作用。考虑到VitD3 + PG结合的这种耐受性作用，进一步的研究将揭示其在人类RA中的合理用途。
