Role of interleukin-6 as a biomarker in diagnosing periprosthetic joint infections: A systematic review

Abstract

Background: Periprosthetic joint infection (PJI) is a serious complication following joint replacement surgeries, with an incidence ranging from 1% to 2% in primary arthroplasties and up to 4% in revision cases. Current diagnostic methods, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), have limitations in specificity and early detection, necessitating the exploration of novel biomarkers like interleukin-6 (IL-6). This systematic review synthesizes data from 50 published studies to evaluate the diagnostic accuracy, sensitivity, and specificity of IL-6 in detecting PJI. Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted in accordance with PRISMA guidelines. We included studies published between 2000 and 2024 that assessed IL-6 levels in patients with suspected PJI. Data regarding IL-6 levels in serum and synovial fluid, diagnostic thresholds, and performance metrics such as sensitivity and specificity were extracted and analyzed. Results: The review included 50 studies comprising a total of 4,500 patients. The pooled sensitivity and specificity of synovial IL-6 were found to be 87% (95% CI: 82%-91%) and 90% (95% CI: 86%-93%), respectively. Serum IL-6 demonstrated a sensitivity of 80% (95% CI: 75%-85%) and specificity of 85% (95% CI: 80%-89%). The optimal synovial fluid cutoff for IL-6 ranged between 3,000-5,000 pg/mL, while serum IL-6 levels exceeding 10 pg/mL were associated with PJI. IL-6 levels correlated strongly with other inflammatory markers, such as CRP and ESR, but showed superior early diagnostic capability. However, variability in IL-6 cutoff values remains a significant challenge. Conclusion: IL-6 is a highly sensitive and specific biomarker for diagnosing PJI, particularly in synovial fluid. Despite its promising diagnostic potential, variability in cutoff values and testing methodologies necessitates further standardization. Combining IL-6 with traditional inflammatory markers may enhance diagnostic accuracy and clinical decision-making. Large-scale, multicenter studies are needed to establish standardized diagnostic protocols.