Objective

To investigate the role of IL-33 in gouty arthritis.

Material

174 Balb/c (wild-type) and 54 ST2^−/− mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels.

Methods

Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM.

Results

Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1β and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1β and TNF-α, and BMDMs from ST2^−/− showed reduced levels of these cytokines after stimulus with MSU crystals.

Conclusion

IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.

中文翻译：

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IL-33增强巨噬细胞释放IL-1β，并促进痛风性关节炎的疼痛和炎症。

目的

调查IL-33在痛风性关节炎中的作用。

材料

在该研究中使用了174只Balb / c（野生型）和54只ST2 ^-/-小鼠。在骨髓源性巨噬细胞（BMDM）中进行了体外实验。来自痛风性关节炎（n  = 7）和骨关节炎（n  = 8）住院患者的滑液样本用于测量IL-33和sST2水平。

方法

痛风是通过在小鼠的膝关节中注射尿酸单钠（MSU）晶体引起的。使用电子von Frey和静态负重轴承确定疼痛程度。通过H＆E染色，Rosenfeld染色载玻片和MPO活性确定嗜中性白细胞的募集。ELISA用于细胞因子和sST2的测量。在BMDM中确定了IL-33的引发作用。

结果

与骨关节炎患者相比，痛风患者的滑液显示出更高的IL-33水平和中性粒细胞计数。在小鼠中，ST2的缺乏防止了机械性疼痛，膝关节水肿，嗜中性白细胞向膝关节募集，并降低了IL-1β和超氧阴离子水平。在巨噬细胞中，IL-33增强了IL-1β和TNF-α的释放，在MSU晶体刺激下，来自ST2 ^-/-的BMDMs降低了这些细胞因子的水平。

结论

IL-33通过刺激MSU晶体刺激巨噬细胞产生细胞因子来介导痛风疼痛和炎症。