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

• Published in: Journal of orthopaedics and traumatology 2017-12, Vol.18 (4), p.349-357
• Main Authors: Panina, Svetlana B., Krolevets, Igor V., Milyutina, Natalia P., Sagakyants, Alexander B., Kornienko, Igor V., Ananyan, Anzhelika A., Zabrodin, Mikhail A., Plotnikov, Andrey A., Vnukov, Valeriy V.
• Format: Article
• Language: English
• Subjects: Adult; Arthritis; Biocompatibility; Biomarkers; Biomarkers - blood; Body mass; Conservative Orthopedics; Correlation; Disease Progression; Enzyme-linked immunosorbent assay; Gout; Humans; Inflammation; Interleukin; Interleukin 18; Interleukin 6; Interleukin-18 - blood; Interleukin-1beta; Interleukin-6 - blood; Knee; Knee Injuries - complications; Leptin; Leptin - blood; Medicine; Medicine & Public Health; Middle Aged; Nitric oxide; Nitric Oxide - blood; Nitrogen oxides; Original; Original Article; Orthopedics; Osteoarthritis; Osteoarthritis, Knee - blood; Osteoarthritis, Knee - diagnostic imaging; Osteoarthritis, Knee - etiology; Patients; Plasma; Post-traumatic knee osteoarthritis; Proinflammatory mediators; Quality; Radiographic severity; Rheumatoid arthritis; Rheumatology; Sensitivity; Sports Medicine; Surgical Orthopedics; Synovial fluid; Synovial Fluid - chemistry; Traumatic Surgery; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-α
• ISSN: 1590-9921; 1590-9999
• DOI: 10.1007/s10195-017-0473-8

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).