Rheumatoid arthritis (RA) is considered a systemic chronic inflammatory joint disease characterized by chronic synovitis and cartilage and bone destruction. Interleukin-33 (IL-33) is a proinflammatory cytokine which is highly expressed in the synovium of RA patients and the joints of mice with collagen-induced arthritis (CIA) and exacerbates CIA in mice. However, the role of the IL-33-neutralizing antibody in the murine model of CIA remains unclear. In the present study, CIA mice were given intraperitoneally with polyclonal rabbit anti-murine IL-33 antibody (anti-IL-33) or normal rabbit IgG control after the first signs of arthritis. Administration of anti-IL-33 after the onset of disease significantly reduced the severity of CIA and joint damage compared with controls treated with normal rabbit IgG. Anti-IL-33 treatment also significantly decreased the serum levels of interferon-γ(IFN-γ),IL-6, IL-12, IL-33, and tumor necrosis factor-α (TNF-α). Moreover, anti-IL-33 treatment significantly downregulated the production of IFN-γ, IL-6, IL-12, IL-33, and TNF-α in ex vivo-stimulated spleen cells. Together, our results indicate that the IL-33-neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines.

中文翻译：

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阻断白细胞介素 33 可减轻小鼠关节炎症并抑制胶原诱导性关节炎的发展

类风湿性关节炎（RA）被认为是一种全身性慢性炎症性关节疾病，其特征是慢性滑膜炎和软骨和骨破坏。白细胞介素-33 (IL-33) 是一种促炎细胞因子，在 RA 患者的滑膜和胶原诱导性关节炎 (CIA) 小鼠的关节中高度表达，并加剧小鼠的 CIA。然而，IL-33 中和抗体在 CIA 小鼠模型中的作用仍不清楚。在本研究中，在出现关节炎的最初迹象后，CIA 小鼠腹腔注射多克隆兔抗鼠 IL-33 抗体（抗 IL-33）或正常兔 IgG 对照。与用正常兔 IgG 治疗的对照相比，疾病发作后施用抗 IL-33 可显着降低 CIA 和关节损伤的严重程度。γ (IFN- γ )、IL-6、IL-12、IL-33 和肿瘤坏死因子-α (TNF- α )。此外，抗 IL-33 治疗显着下调了体外刺激的脾细胞中 IFN- γ、IL-6、IL-12、IL-33 和 TNF - α 的产生。总之，我们的结果表明 IL-33 中和抗体可能通过抑制促炎细胞因子的释放为 RA 提供治疗策略。