The role of interleukin-1 in the pathogenesis of rheumatoid arthritis
The role of interleukin-1 in the pathogenesis of rheumatoid arthritis
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DOI：
10.1093/rheumatology/keh201
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发表时间：
2004-06-01
期刊：
影响因子：
5.5
通讯作者：
Calabrese, L.
中科院分区：
文献类型：
--
作者：
Kay, J.;Calabrese, L.
大量实验证据表明促炎细胞因子 IL-1 与 RA 的发病机制有关。例如，兔膝关节中 IL-1 β 过度表达会导致具有 RA 临床和组织学特征的关节炎，而 IL-1 缺乏则与关节损伤减少有关。在实验模型中，IL-1 阻滞剂，包括 IL-1 受体拮抗剂 (IL-1Ra)，可显着降低临床和组织学疾病参数。在 RA 患者中，血浆和滑液中 IL-1 的浓度升高，并且这些与疾病活动的各种参数相关。然而，内源性 IL-1Ra 的产生似乎不足以平衡这些较高的 IL-1 水平。阿那白滞素 (anakinra)（一种重组人 IL-1Ra (r-metHuIL-1ra)）的对照临床试验已证实阻断 IL-1 对活动性 RA 患者的功效。与安慰剂相比，当单独使用或与甲氨蝶呤联合使用时，阿那白滞素可显着减轻 RA 的临床体征和症状。综上所述，这些结果表明IL-1在RA的发病机制中发挥着重要作用。
A significant body of experimental evidence has implicated the proinflammatory cytokine IL-1 in the pathogenesis of RA. For example, IL-1 beta overexpression in rabbit knee joints causes arthritis with clinical and histological features characteristic of RA, whereas IL-1 deficiency is associated with reduced joint damage. In experimental models, IL-1 blockers, including IL-1 receptor antagonist (IL-1Ra), significantly reduce clinical and histological disease parameters. In RA patients, plasma and synovial fluid concentrations of IL-1 are elevated, and these correlate with various parameters of disease activity. The production of endogenous IL-1Ra, however, appears to be insufficient to balance these higher IL-1 levels. The efficacy of blocking IL-1 in patients with active RA has been established in controlled clinical trials of anakinra, a recombinant human IL-1Ra (r-metHuIL-1ra). When used alone or in combination with methotrexate, anakinra significantly reduces the clinical signs and symptoms of RA compared with placebo. Taken together, these results indicate that IL-1 plays an important role in the pathogenesis of RA.