Atzeni Fabiola, Ventura Donatella, Batticciotto Alberto, Boccassini Laura, Sarzi-Puttini Piercarlo
Experimental Medicine, Queen Mary University of London, London, UK.
J Rheumatol Suppl. 2012 Jul;89:97-9. doi: 10.3899/jrheum.120256.
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of unknown etiology that is associated with psoriasis. Joint destruction is often progressive: almost half of the patients attending an early arthritis clinic showed radiological damage 2 years after diagnosis. Proinflammatory cytokines are major mediators of systemic and local inflammation, and high levels of interleukin 1 (IL-1), IL-6, and tumor necrosis factor have been found in psoriatic skin lesions and the synovial tissue of patients with rheumatoid arthritis and PsA. IL-6 is a pleiotropic cytokine that mainly signals by membrane (neutrophil and lymphocyte) or soluble (endothelial cell) IL-6 receptors. IL-6 was originally identified as a factor in B cell differentiation, but is now known to influence T cell development: in the presence of IL-6 and transforming growth factor-ß (TGF-ß), naive T cells develop into Th17 cells, which are important mediators in PsA. IL-6 may also directly contribute to the epidermal hyperplasia seen in psoriatic epithelium and affect the function of dermal inflammatory cells. However, there are no data concerning the use of tocilizumab in patients with PsA, although a pilot study is currently being carried out because the role of IL-6 in the pathogenesis of PsA supports the idea that targeted treatments against IL-6 might be effective.
银屑病关节炎(PsA)是一种病因不明的慢性炎症性关节病,与银屑病相关。关节破坏通常呈进行性发展:在一家早期关节炎诊所就诊的患者中,近一半在诊断后2年出现了放射学损伤。促炎细胞因子是全身和局部炎症的主要介质,在银屑病皮损以及类风湿关节炎和PsA患者的滑膜组织中发现了高水平的白细胞介素1(IL-1)、IL-6和肿瘤坏死因子。IL-6是一种多效性细胞因子,主要通过膜性(中性粒细胞和淋巴细胞)或可溶性(内皮细胞)IL-6受体进行信号传导。IL-6最初被鉴定为B细胞分化因子,但现在已知其会影响T细胞发育:在IL-6和转化生长因子-β(TGF-β)存在的情况下,初始T细胞会发育为Th17细胞,而Th17细胞是PsA的重要介质。IL-6也可能直接导致银屑病上皮中出现的表皮增生,并影响真皮炎症细胞的功能。然而,目前尚无关于托珠单抗在PsA患者中应用的数据,尽管目前正在进行一项试点研究,因为IL-6在PsA发病机制中的作用支持了针对IL-6的靶向治疗可能有效的观点。