Protective effect of eotaxin-2 inhibition in adjuvant-induced arthritis
Protective effect of eotaxin-2 inhibition in adjuvant-induced arthritis
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DOI：
10.1111/j.1365-2249.2010.04172.x
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发表时间：
2010-08-01
影响因子：
4.6
通讯作者：
Barshack, I.
中科院分区：
文献类型：
--
作者：
Ablin, J. N.;Entin-Meer, M.;Barshack, I.
Eotaxin-2是一种有效的嗜酸性粒细胞、嗜碱性粒细胞和辅助T型2 （Th2）淋巴细胞的化学引诱剂。eotaxin-2/CCL24受体CCR3在人脑、皮肤、内皮细胞和巨噬细胞中表达。本研究的目的是评估单克隆抗eotaxin-2抗体对大鼠佐剂性关节炎（AIA）发展的保护作用。采用不完全弗氏佐剂+结核分枝杆菌皮内注射诱导Lewis大鼠佐剂性关节炎。大鼠腹腔注射抗eotaxin-2 （G7、G8、D8）单克隆抗体，每周3次。对照组用小鼠总免疫球蛋白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、全动物活动能力和体重来评估关节炎严重程度。取关节样本进行病理评估，死后进行踝关节x线检查以记录糜烂情况。与用免疫球蛋白或PBS治疗的大鼠相比，用抗eotaxin-2抗体治疗的大鼠对关节炎有明显的抑制作用。抑制作用在踝关节直径、关节炎评分和活动度评分中表现明显。标记为D8的抗体效果最好。在出现关节炎之前治疗的动物和在关节炎症发展后开始治疗的动物都观察到这种效果。D8和MTX联合治疗可产生额外的保护作用。病理和x线检查也显示d8治疗动物的炎症明显减轻。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提供新的治疗靶点。
P>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.