Adorini Luciano, Penna Giuseppe
Intercept Pharmaceuticals, Corciano (Perugia), Italy.
Nat Clin Pract Rheumatol. 2008 Aug;4(8):404-12. doi: 10.1038/ncprheum0855. Epub 2008 Jul 1.
1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the biologically active form of vitamin D(3), is a secosteroid hormone essential for bone and mineral homeostasis. It regulates the growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory properties. Cells involved in innate and adaptive immune responses--including macrophages, dendritic cells, T cells and B cells--express the vitamin D receptor (VDR), and can both produce and respond to 1,25(OH)(2)D(3). The net effect of the vitamin D system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity. Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases, and clarification of the physiological role of endogenous VDR agonists in the regulation of autoimmune responses will guide the development of pharmacological VDR agonists for use in the clinic. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of autoimmune diseases, from rheumatoid arthritis to systemic lupus erythematosus, and possibly also multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune prostatitis.
1,25-二羟基维生素D(3)[1,25(OH)(2)D(3)]是维生素D(3)的生物活性形式，是一种对骨骼和矿物质稳态至关重要的甾醇类激素。它调节多种细胞类型的生长和分化，并具有免疫调节和抗炎特性。参与先天性和适应性免疫反应的细胞——包括巨噬细胞、树突状细胞、T细胞和B细胞——表达维生素D受体(VDR)，并且既能产生1,25(OH)(2)D(3)，也能对其作出反应。维生素D系统对免疫反应的净效应是增强先天性免疫并对适应性免疫进行多方面调节。流行病学证据表明维生素D缺乏与几种自身免疫性疾病发病率增加之间存在显著关联，阐明内源性VDR激动剂在自身免疫反应调节中的生理作用将指导临床上使用的药理学VDR激动剂的开发。合成VDR激动剂的抗增殖、促分化、抗菌、免疫调节和抗炎特性可用于治疗从类风湿性关节炎到系统性红斑狼疮等多种自身免疫性疾病，也可能用于治疗多发性硬化症、1型糖尿病、炎症性肠病和自身免疫性前列腺炎。
