Chimeric anti-IL-17 full-length monoclonal antibody is a novel potential candidate for the treatment of rheumatoid arthritis
Chimeric anti-IL-17 full-length monoclonal antibody is a novel potential candidate for the treatment of rheumatoid arthritis
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DOI：
10.3892/ijmm.2013.1611
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发表时间：
2014-03-01
影响因子：
5.4
通讯作者：
Li, Deshan
中科院分区：
文献类型：
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作者：
Bai, Fuliang;Tian, Hui;Li, Deshan
类风湿性关节炎（RA）是一种自身免疫性疾病，主要表现为炎症性关节炎。它与滑膜关节的慢性炎症（主要发生在手和脚）以及全身性关节外炎症有关。嵌合抗白细胞介素 (IL)-17 全长单克隆抗体 (CMa17Aab) 靶向 IL-17A，IL-17A 是 RA 和其他炎症性疾病发病机制中的重要细胞因子。在这项研究中，我们研究了 CMa17Aab 是否对 II 型胶原诱导关节炎 (CIA) 小鼠模型发挥治疗作用。患有 CIA 的小鼠皮下注射人源化 CMa17Aab 抗体。通过估计关节炎严重程度评分、组织学损伤和骨质破坏的程度、自身反应性体液和细胞免疫反应以及细胞因子的产生来评估治疗效果。 CMa17Aab 治疗对 CIA 小鼠的临床和组织学参数产生了有益的影响。与对照组相比，CMa17Aab治疗可显着减轻关节炎症状的严重程度，预防骨损伤和软骨破坏，减少体液和细胞免疫反应，下调IL-6、IL-8、基质金属蛋白酶（MMP）-3、IL-17、IL-1β、肿瘤坏死因子的表达 (TNF)-α、发炎组织中核因子 kappa B 配体 (RANKL) 和干扰素 (IFN)-gamma 的受体激活剂。总之，我们的研究表明，CMa17Aab 治疗可通过预防关节炎症、软骨破坏和骨损伤，对患有 CIA 的小鼠发挥有益作用。这些初步结果表明，CMa17Aab 是 RA 中的重要调节剂，并且它可能代表一种新的治疗剂，可能在治疗这种疾病中有用。
Rheumatoid arthritis (RA) is an autoimmune disease, primarily manifesting as inflammatory arthritis. It is associated with chronic inflammation of the synovial joints, mostly in the hands and feet, as well as with systemic extra-articular inflammation. The chimeric anti-interleukin (IL)-17 full-length monoclonal antibody (CMa17Aab) targets IL-17A, which is an important cytokine in the pathogenesis of RA and other inflammatory disorders. In this study, we investigated whether CMa17Aab exerts therapeutic effects in a mouse model of type II collagen-induced arthritis (CIA). Mice with CIA were subcutaneously injected with the humanized CMa17Aab antibody. The effects of treatment were assessed by estimating the arthritis severity score, the extent of histological damage and bone destruction, the autoreactive humoral and cellular immune responses and the production of cytokines. Treatment with CMa17Aab exerted beneficial effects in the mice with CIA as regards clinical and histological parameters. Compared with the controls, treatment with CMa17Aab resulted in a significant alleviation of the severity of the symptoms of arthritis, by preventing bone damage and cartilage destruction, reducing humoral and cellular immune responses, and downregulating the expression of IL-6, IL-8, matrix metalloproteinase (MMP)-3, IL-17, IL-1 beta, tumor necrosis factor (TNF)-alpha, receptor activator for nuclear factor-kappa B ligand (RANKL) and interferon (IFN)-gamma in inflamed tissues. In conclusion, our study demonstrates that treatment with CMa17Aab exerts beneficial effects in mice with CIA, by preventing joint inflammation, cartilage destruction and bone damage. These preliminary results suggest that CMa17Aab is an important regulator in RA, and that it may represent a novel therapeutic agent that may prove useful in the treatment of this disease.