Suitability of serum cytokine profiling for early diagnosis of implant-associated infections after orthopaedic surgery: A preliminary prospective study

Abstract The C-reactive protein (CRP) is still the conventional marker used to diagnose implant-associated infections (IAI) after orthopaedic surgery. However, the CRP level can lead to misdiagnosis since it is up-regulated not only during bacterial infection. In this prospective study, we evaluated the serum cytokine profile before (pre-OP) and after orthopaedic surgery (post-OP) as well as after confirmation of a developed infection (COI) to identify candidate biomarkers for diagnosis of IAI. Sera from 10 controls 7 to 1 days pre-OP and 0 to 22 days post-OP as well as from 5 patients who developed IAI 5 to 1 days pre-OP, 0 to 197 days post-OP and after COI were analyzed for 27 different cytokines using a multiplex cytokine assay. In addition to CRP, 14 cytokines IL-1ra, IL-4, IL-5, IL-6, IL-8, IL-12(p70), IL-13, IL-17, eotaxin, G-CSF, IFN-γ, IP-10, MCP-1, and MIP-1β were significantly altered (P ≤ 0.05) during the study although some differences were low-fold elevations compared to the pre-OP levels. IL-6 as well as IL-12(p70) were consistently elevated in infected patients. Surgery influenced cytokine production with some overlap of cytokines in both groups, implying that the use of cytokines is maximized when the cytokines are not or no longer affected by surgical trauma. To lend more robustness to the selection of candidate cytokines, in addition to the statistical differences, we applied a threshold cut-off of approximately 2-fold elevations when comparisons were made. This resulted in the selection of 8 cytokines, namely IL-6, IL-1ra, IL-8, IL-12(p70), eotaxin, IP-10, MCP-1, and MIP-1β, which may be used in a multiplex assay for detection of IAI after surgery. Furthermore, IL-1ra and IL-8 may be used as prognostic cytokines prior to surgery. The present results imply that the use of cytokines may be a suitable alternative to CRP for IAI diagnosis.