Gonzalez-Rey Elena, Chorny Alejo, Del Moral Raimundo G, Varela Nieves, Delgado Mario
Department of Biochemistry and Molecular Biology, Medical School of Seville, Seville, Spain.
Ann Rheum Dis. 2007 May;66(5):582-8. doi: 10.1136/ard.2006.062703. Epub 2006 Dec 6.
Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone.
To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions.
DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies.
Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease-that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor beta1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis.
This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.
类风湿性关节炎是一种病因不明的慢性自身免疫性疾病，其特征为关节慢性炎症以及随后的软骨和骨破坏。
基于施用可的他汀（一种新发现的具有抗炎作用的神经肽）提出一种治疗关节炎的新策略。
对胶原诱导性关节炎的DBA/1J小鼠在疾病发作后用可的他汀进行治疗，并评估临床评分和关节组织病理学。通过测量关节和血清中各种炎症介质（细胞因子和趋化因子）的水平来确定炎症反应。通过确定用胶原刺激的引流淋巴结细胞的增殖反应和细胞因子谱以及检测血清自身抗体的含量来评估1型辅助性T细胞（Th1）介导的自身反应性。
可的他汀治疗显著降低了已建立的胶原诱导性关节炎的严重程度，完全消除了关节肿胀以及软骨和骨的破坏。可的他汀的治疗效果与该疾病的两个有害成分的显著降低有关，即Th1驱动的自身免疫和炎症反应。可的他汀下调了各种炎症细胞因子和趋化因子的产生，减少了抗原特异性Th1细胞的扩增，并诱导了调节性细胞因子如白细胞介素10和转化生长因子β1的产生。可的他汀通过生长抑素和胃饥饿素受体对滑膜细胞发挥作用，其效果比这两种肽预防实验性关节炎的效果都要高。
这项工作为评估可的他汀作为类风湿性关节炎新治疗方法的疗效提供了有力的理论依据。
