Background: Meniscal injuries trigger a local inflammatory response mediated by intra-articular mediators. Proinflammatory cytokines and chemokines can lead to cartilage degradation and subchondral bone changes, contributing to posttraumatic osteoarthritis. The role that age plays in this inflammatory response is unclear. Purpose: To investigate age-dependent variation in cytokine types and concentrations in knee synovial fluid after meniscal injury. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing arthroscopic knee surgery for isolated meniscal injury were prospectively enrolled between July 2011 and April 2024. Synovial fluid was aspirated from the operative knee, and concentrations of 10 biomarkers were measured. Patients at least 9 years after surgery were invited to complete patient-reported outcome (PRO) surveys. Multivariable linear regression assessed pairwise relationships between age at surgery, log-normalized biomarker concentrations, and PROs, while adjusting for relevant covariates. Conditional process analysis was used to explore age-biomarker relationships, with symptom duration as a moderator and baseline Outerbridge grade as a mediator. Results: The study included 160 patients for biomarker analysis with a mean ± SD age of 50.2 ± 12.5 years. Forty-seven patients who reached a minimum 9 years of follow-up completed PRO surveys. Mean follow-up was 10.2 ± 1.3 years. Regression analysis revealed positive associations between age and log-normalized concentration of preoperative IL-6. Moderator analysis found age to be positively associated with IL-6, VEG-F, and IL-1Ra in chronic meniscal injuries. Mediator analysis found an indirect positive relationship between age and MIP-B, VEGF, and MMP-3 and an indirect negative relationship between age and TIMP-1 and TIMP-2. Preoperative TIMP-1 was positively associated with 10-year Knee injury and Osteoarthritis Outcome Score–Physical Function Short Form score and elevated in treatment responders. Conclusion: Age at surgery was associated with higher concentrations of proinflammatory biomarkers and lower concentrations of anti-inflammatory biomarkers in the synovial fluid before meniscal surgery. Anti-inflammatory markers were associated with improved long-term PROs. These findings suggest an age-related intensification of the proinflammatory response and inhibition of the anti-inflammatory response that may contribute to long-term functional decline in older patients after meniscal surgery. There is potential for age-specific immunomodulatory therapeutic strategies to manage inflammation and mitigate the progression toward posttraumatic osteoarthritis in older patients.

中文翻译：

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半月板损伤后膝关节滑液细胞因子类型和浓度的年龄依赖性变化

背景： 半月板损伤触发由关节内介质介导的局部炎症反应。促炎细胞因子和趋化因子可导致软骨降解和软骨下骨变化，从而导致创伤后骨关节炎。年龄在这种炎症反应中的作用尚不清楚。目的： 研究半月板损伤后膝关节滑液中细胞因子类型和浓度的年龄依赖性变化。研究设计：队列研究;证据水平，3.方法： 前瞻性纳入 2011 年 7 月至 2024 年 4 月期间接受关节镜膝关节手术治疗孤立性半月板损伤的患者。从手术膝关节抽吸滑液，并测量 10 种生物标志物的浓度。邀请术后至少 9 年的患者完成患者报告结果 （PRO） 调查。多变量线性回归评估了手术年龄、对数标准化生物标志物浓度和 PRO 之间的成对关系，同时调整了相关协变量。条件过程分析用于探索年龄-生物标志物关系，以症状持续时间为调节因素，基线 Outerbridge 等级为中介因素。结果： 该研究包括 160 例患者进行生物标志物分析，平均 ± SD 年龄为 50.2 ± 12.5 岁。47 名随访至少 9 年的患者完成了 PRO 调查。平均随访时间为 10.2 ± 1.3 年。回归分析显示年龄与术前 IL-6 的对数标准化浓度呈正相关。调节器分析发现，在慢性半月板损伤中，年龄与 IL-6 、 VEG-F 和 IL-1Ra 呈正相关。 介质分析发现，年龄与 MIP-B 、 VEGF 和 MMP-3 之间存在间接正相关，年龄与 TIMP-1 和 TIMP-2 之间存在间接负相关。术前 TIMP-1 与 10 年膝关节损伤和骨关节炎结果评分-身体功能简表评分呈正相关，并且在治疗反应者中升高。结论： 手术年龄与半月板手术前滑液中促炎生物标志物浓度较高和抗炎生物标志物浓度较低相关。抗炎标志物与长期 PRO 的改善相关。这些发现表明，与年龄相关的促炎反应增强和抗炎反应的抑制可能导致半月板手术后老年患者长期功能下降。年龄特异性免疫调节治疗策略有可能控制老年患者的炎症并减轻向创伤后骨关节炎的进展。