Effect of Inflammatory Biomarkers on Patient Symptomatic State at Time of Knee Chondroplasty

In patients undergoing knee arthroscopy for chondral defects, the influence of cytokines on patient pain and function is not fully understood.

To investigate the concentrations of synovial inflammatory cytokines in patients undergoing arthroscopic chondroplasty for chondral defects in the knee and correlate those cytokine levels with baseline patient-reported outcome measures (PROMs) and defect characteristics.

Case series; Level of evidence, 4.

Patients undergoing arthroscopic chondroplasty for knee cartilage defects were assigned preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee International Knee Documentation Committee (IKDC) Subjective Knee Forms. All patients received a successful synovial fluid aspiration just before initiation of the arthroscopic procedure, and concentrations of 11 cytokines of interest were measured. The number of defects, total defect area, and International Cartilage Regeneration & Joint Preservation Society (ICRS) grades were recorded based on intraoperative assessment. Univariate correlation testing was used to assess significance between cartilage defect characteristics, PROM scores, and cytokine concentrations. The Akaike information criterion was used to select the best-fit multivariate regression model to determine the primary influence on baseline PROMs.

A total of 60 patients age 18 to 55 years were included. Matrix metalloproteinase 1 (MMP-1) had a positive correlation with number of defects treated (P = .016) and negative correlation with KOOS Quality of Life (QOL) subscale scores (P = .035; R² = 0.173). Vascular endothelial growth factor (VEGF) was positively correlated with defects treated (P = .005) and negatively correlated with KOOS Symptoms scores (P = .035; R² = 0.225). The treatment of multiple defects was an independent predictor of elevated interleukin 1α (IL-1α) (P = .002; R² = 0.202). C-C chemokine ligand 2 (CCL-2) was positively correlated with multiple defects (P = .012) and negatively with KOOS QOL (P = .016; R² = 0.173). Female sex was correlated with higher concentrations of MMP-3 (P = .007; R² = 0.144), fibroblast growth factor 2 (FGF-2) (P = .012; R² = 0.178), and bone morphogenetic protein 2 (BMP-2) (P = .008; R² = 0.169). BMP-2 was negatively correlated with KOOS Symptoms (P = .019). The primary driver of preoperative KOOS Symptoms scores on multivariate analysis was VEGF (P = .023; R² = 0.120). Similarly, KOOS QOL was independently correlated with MMP-1 concentration (P = .045; R² = 0.079).

Elevated MMP-1 was the primary driver of worse preoperative KOOS QOL scores on multivariate analysis, more so than defect characteristics. Similarly, worse preoperative KOOS Symptoms scores were more strongly correlated with elevated VEGF concentrations rather than defect ICRS grades. Other individual factors such as a larger number of defects and female sex were independently correlated with a more inflammatory synovial profile of the patient.