Introduction. Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma. Materials and Methods. In this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a value below 0.05 was considered significant. Results. Compared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF, IFNγ, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-β1 and TGF-β2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFNγ, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated. Conclusions. We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was “retrospectively registered” on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.

中文翻译：

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踝关节内骨折后炎症细胞因子和蛋白质升高：47 例踝关节骨折患者的横断面研究

介绍。关节内骨折是踝关节创伤后骨关节炎 (PTOA) 的主要病因。关节内骨折后促炎细胞因子的升高可能导致滑膜分解代谢和软骨退化。我们旨在比较受伤和健康踝关节中的细胞因子水平，检查踝关节骨折的长期细胞因子水平，并研究骨折踝关节和血浆中细胞因子水平之间的关联。材料和方法。在这项横断面研究中，在手术前收集了 47 名急性关节内踝关节骨折患者和 8 名接受植入物移除的患者的滑液 (SF) 和血浆。我们确定了 16 种炎性细胞因子、2 种软骨降解蛋白和 4 种代谢蛋白的浓度，并将急性受伤的脚踝与健康对侧或金属去除期间的水平进行了比较。还将受伤脚踝中的细胞因子水平与血清​​细胞因子水平进行了比较。非参数 Wilcoxon 秩和检验和 Spearman 检验用于统计分析，低于 0.05 的值被认为是显着的。结果. 与健康的踝关节相比，急性关节内骨折的踝关节滑液中的几种促炎细胞因子和蛋白酶（IL- 1β、IL-2、IL-6、IL-8、IL-12p70、TNF、 IFN γ、MMP-1、MMP-3 和 MMP-9）和抗炎细胞因子（IL-1RA、IL-4、IL-10 和 IL-13）。软骨降解产物（ACG、CTX-2）和代谢介质（TGF- β1和TGF- β2）的水平也显着升高。ACG、IL-12-p70、IFN γ、IL-4 和 bFGF 的滑膜浓度与血清水平相关。虽然大多数检查的滑膜细胞因子在植入物移除后没有变化，但 IL-4 和 IL-6 水平上调。结论. 我们表明，急性踝关节骨折后会出现炎症反应和软骨退化。这些数据有助于目前对 PTOA 发展背后的蛋白质调控的理解，并且是朝着补充当前手术治疗的又一步。这项横断面研究于 2017 年 10 月 31 日在 ClinicalTrials.gov (NCT03769909) 上“回顾性注册”。注册是在纳入第一位患者之后和完成患者招募和统计分析之前进行的：https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1。