Sourasky Medical Center, Rheumatology Institute, Tel-Aviv University, Tel-Aviv, Israel.
Clin Exp Immunol. 2010 Aug;161(2):276-83. doi: 10.1111/j.1365-2249.2010.04172.x. Epub 2010 May 7.
Eotaxin-2 is a potent chemoattractant for eosinophils, basophils and T helper type 2 (Th2) lymphocytes. The eotaxin-2/CCL24 receptor CCR3 is expressed in human brain, skin, endothelium and macrophages. The aim of the current study was to evaluate the protective effect of a monoclonal anti-eotaxin-2 antibody on the development of adjuvant-induced arthritis in rats (AIA). Adjuvant arthritis was induced in Lewis rats by intradermal injection of incomplete Freund's adjuvant +Mycobacterium tuberculosis. Rats were treated by intraperitoneal (i.p.) injection with three monoclonal antibodies against eotaxin-2 (G7, G8, D8) three times per week. Controls were treated with total mouse immunoglobulin G (IgG), methotrexate (MTX) or phosphate-buffered saline (PBS). Arthritis severity was evaluated by measuring ankle swelling, arthritic score, whole animal mobility and body weight. Sample joints were obtained for pathological evaluation and postmortem X-ray of ankle joints was performed to document erosions. Significant inhibition of arthritis was observed in rats treated with anti-eotaxin-2 antibodies compared to those treated with immunoglobulin or PBS. Inhibition was manifest in ankle diameter, arthritic score and mobility score. The antibody marked D8 showed the greatest efficacy. The effect was observed both in animals treated before the appearance of arthritis and in those where treatment was begun after development of joint inflammation. Combined treatment with D8 and MTX caused additional protection. Significant reduction of inflammation in D8-treated animals was also demonstrated in pathological and X-ray examinations. Inhibition of eotaxin-2 by monoclonal antibodies has a significant protective effect in adjuvant arthritis. These results may introduce a novel therapeutic target in rheumatoid arthritis and additional inflammatory joint disorders.
趋化因子 Eotaxin-2 是嗜酸性粒细胞、嗜碱性粒细胞和辅助性 T 细胞 2（Th2）淋巴细胞的有效趋化因子。趋化因子 Eotaxin-2/CCL24 受体 CCR3 表达于人脑、皮肤、内皮细胞和巨噬细胞中。本研究旨在评估单克隆抗 Eotaxin-2 抗体对弗氏不完全佐剂+结核分枝杆菌诱导的大鼠关节炎（AIA）发展的保护作用。通过皮内注射不完全弗氏佐剂+结核分枝杆菌诱导 Lewis 大鼠关节炎。大鼠每周通过腹腔内（i.p.）注射三种抗 Eotaxin-2 单克隆抗体（G7、G8、D8）进行治疗。对照组用总鼠免疫球蛋白 G（IgG）、甲氨蝶呤（MTX）或磷酸盐缓冲盐水（PBS）治疗。通过测量踝关节肿胀、关节炎评分、整体动物活动度和体重来评估关节炎严重程度。获取关节样本进行病理评估，并对踝关节进行死后 X 射线检查以记录侵蚀情况。与 IgG 或 PBS 治疗的大鼠相比，用抗 Eotaxin-2 抗体治疗的大鼠关节炎明显受到抑制。抑制表现在踝关节直径、关节炎评分和活动评分上。抗体 D8 显示出最大的疗效。在关节炎出现之前开始治疗的动物和在关节炎症发展后开始治疗的动物中均观察到该效果。D8 与 MTX 联合治疗可进一步保护。在 D8 治疗的动物中，病理学和 X 射线检查也显示出炎症明显减轻。单克隆抗体抑制 Eotaxin-2 对佐剂性关节炎有显著的保护作用。这些结果可能为类风湿关节炎和其他炎症性关节疾病引入新的治疗靶点。
