Summary

Age at surgery is associated with higher concentrations of specific pro-inflammatory cytokines IL-6 and MCP-1 in the synovial fluid following meniscal injury, suggesting an age-dependent intensification of the inflammatory response.

Abstract

Purpose

Meniscal injuries trigger an acute inflammatory response mediated by intra-articular cytokines, which can accelerate cartilage degradation and subchondral bone changes, contributing to post-traumatic osteoarthritis (PTOA). The role of age in this inflammatory response is unclear. The current study investigates the variation in cytokine types and concentrations in knee synovial fluid following meniscal injury across different age groups.

Methods

Patients undergoing arthroscopic knee surgery were prospectively enrolled in the study between July 2011 and November 2022. Synovial fluid was aspirated from the operative knee before surgical incision and the concentrations of 10 biomarkers of interest (RANTES, IL-6, MCP-1, MIP-B, VEGF, TIMP-1, TIMP-2,IL-1RA, MMP-3, and bFGF) were measured by immunoassay. Those who had isolated meniscal injury were retrospectively identified and included for analysis. Patients completed VAS Pain, Lysholm, Tegner, and KOOS-PS surveys at 10-year follow-up. Multivariable linear regression was performed to assess the relationship between age at surgery and each log-normalized biomarker concentration while controlling for sex and body mass index. Regression of age against each patient-reported outcome score was performed in the same fashion.

Results

The study included 160 patients (86 males and 74 females) for biomarker analysis with a mean age of 50.2 years ± 12.5. Regression analysis identified positive associations between age and log-normalized concentrations of IL-6 (p = 0.008, beta = 0.216) and MCP-1 (p = 0.022, beta = 0.187). Of these patients, 47 completed 10-year PRO follow-up and were included in subsequent analysis. Mean follow-up time was 10.2 ± 1.3 years. Age was negatively associated with Tegner score at 10 years post-operatively (p = 0.002, beta = -0.445). There were no other significant associations between age and PROs. Increased TIMP-1 was associated with improved KOOS-PS (p = 0.013, beta = 0.346).

Conclusion

Age at surgery is associated with higher concentrations of specific pro-inflammatory cytokines IL-6 and MCP-1 in the synovial fluid following meniscal injury, suggesting an age-dependent intensification of the inflammatory response. When coupled with the negative effect of age on Tegner scores at long-term follow-up, this pattern aligns with the theory of "inflammaging," where aging is accompanied by a chronic, low-grade inflammation that may exacerbate joint degeneration and negatively impact recovery and the outcome of surgery. Notably, higher levels of TIMP-1, an anti-inflammatory cytokine, were linked to better KOOS-PS outcomes, underscoring the protective role of anti-inflammatory mediators and their potential as therapeutic targets for improving long-term recovery. These findings highlight the need for age-specific therapeutic strategies to manage inflammation and potentially mitigate the progression toward post-traumatic osteoarthritis in the older patient population with symptomatic meniscus injury.