T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis.
T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in collagen-induced arthritis.
复制标题
T-614 是一种新型免疫调节剂，可减轻胶原诱导的关节炎中的关节炎症和关节损伤。
DOI：
10.1186/ar2554
复制
发表时间：
2008
影响因子：
4.9
通讯作者：
Bao CD
中科院分区：
文献类型：
--
作者：
Du F;Lü LJ;Fu Q;Dai M;Teng JL;Fan W;Chen SL;Ye P;Shen N;Huang XF;Qian J;Bao CD
T-614是一种新型口服抗风湿药，用于治疗类风湿关节炎。它是否具有免疫调节或疾病修饰特性及其作用机制在很大程度上尚未确定。胶原诱导性关节炎（CIA）大鼠每日接受T-614（5和20 mg/kg）治疗。接受甲氨蝶呤（每3天1 mg/kg）和非甾体抗炎药尼美舒利（每天10 mg/kg）的动物用作对照。联合治疗组接受T-614（10 mg/kg/天）和甲氨蝶呤（1 mg/kg/3天）治疗。评价后爪肿胀并计算放射学评分。通过Bio-plex分析评估血清细胞因子水平。使用定量PCR评估干扰素-γ、IL-4和IL-17的mRNA表达。采用ELISA法测定血清IL-17和抗II型胶原抗体（总IgG、IgG 1、IgG 2a、IgG 2b和IgM）。口服T-614可抑制足肿胀，并对关节炎诱导的软骨和骨侵蚀提供显著保护，与甲氨蝶呤的作用相当。用T-614处理的CIA大鼠表现出外周血单个核细胞和淋巴结细胞中IL-17 mRNA表达的降低，以及循环IL-17以剂量依赖性方式降低。T-614还可降低血清肿瘤坏死因子-α、IL-1β和IL-6水平。甲氨蝶呤和T-614的组合观察到协同效应。此外，T-614（20 mg/kg/天）抑制抗II型胶原抗体的产生，并对体内IgG 2a亚类水平产生差异性影响，而IgM水平降低，IgG 1水平无任何变化。总之，这里提出的研究结果表明，新的药物T-614对实验性关节炎具有疾病修饰作用，而不是尼美舒利。我们的数据表明，T-614是一种有效的疾病修饰剂，可以防止CIA大鼠的骨/软骨破坏和炎症。与甲氨蝶呤联合显著增强T-614的治疗效果。
T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined. Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-γ, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG1, IgG2a, IgG2b and IgM) were measured using ELISA. Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-α, IL-1β and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG1 level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide. Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats. Combination with methotrexate markedly enhances the therapeutic effect of T-614.
登录
查看更多内容
影响因子：
4.9
作者：
Hwang SY;Kim JY;Kim KW;Park MK;Moon Y;Kim WU;Kim HY
通讯作者：
Kim HY
影响因子：
4.9
作者：
Kehlen A;Pachnio A;Thiele K;Langner J
通讯作者：
Langner J
影响因子：
3.8
作者：
Chabaud, M;Garnero, P;Miossec, P
通讯作者：
Miossec, P
影响因子：
4.9
作者：
Andreas, Kristin;Luebke, Carsten;Sittinger, Michael
通讯作者：
Sittinger, Michael
类风湿关节炎中滑膜细胞。树突状细胞。
影响因子：
4.9
作者：
Lutzky, Viviana;Hannawi, Suad;Thomas, Ranjeny
通讯作者：
Thomas, Ranjeny