Circulating levels of proinflammatory mediators as potential biomarkers of post-traumatic knee osteoarthritis development

BACKGROUND: The identification of biomarkers of post-traumatic osteoarthritis (PTOA) progression is of clinical importance. The aims of this study were: (1) to assess the abilities of various soluble proinflammatory mediators in plasma to distinguish patients with knee PTOA from controls; (2) to determine the correlations between the mediators in plasma and those mediators in synovial fluid (SF); and (3) to explore the associations of the mediators with radiographic PTOA severity. MATERIALS AND METHODS: The concentrations of IL-1β, IL-6, IL-18, TNFα, and leptin were measured using ELISA. Nitric oxide was determined as nitrite/nitrate (NO(x)) using the Griess reaction. RESULTS: We included 171 subjects (134 PTOA patients and 37 controls) and excluded patients with rheumatoid arthritis or gout. The ROC curve of plasma NO(x) had the highest AUC, a specificity of 100%, and a sensitivity of 84.4%. The combination of IL-6 and leptin proved to be the most discriminatory, with an AUC value of 0.933, a specificity of 96.7%, and a sensitivity of 85.7%. The levels of NO(x), IL-6, IL-18, and leptin in plasma were significantly correlated with their levels in SF. Leptin levels in both plasma (p = 0.036) and SF (p = 0.041) and the synovial IL-18 level (p = 0.045) were correlated with the Kellgren–Lawrence (KL) grade. Early-stage PTOA (KL 1–2) was associated with a high concentration of IL-1β in plasma before and after (OR 6.235, 95% CI 1.362 to 28.552, p = 0.018) adjusting for age, gender, and BMI. CONCLUSIONS: Circulating NO(x) level and a combination of IL-6 and leptin permitted the strongest discrimination of patients with PTOA from controls. PTOA severity was correlated with leptin levels in plasma and SF and with the synovial IL-18 level. Early PTOA was associated with the circulating level of IL-1β. LEVEL OF EVIDENCE: III (case–control study).