Impact of Cytokines and Phosphoproteins in Response to Chronic Joint Infection

The early cellular response to infection has been investigated extensively, generating valuable information regarding the mediators of acute infection response. Various cytokines have been highlighted for their critical roles, and the actions of these cytokines are related to intracellular phosphorylation changes to promote infection resolution. However, the development of chronic infections has not been thoroughly investigated. While it is known that wound healing processes are disrupted, the interactions of cytokines and phosphoproteins that contribute to this dysregulation are not well understood. To investigate these relationships, this study used a network centrality approach to assess the impact of individual cytokines and phosphoproteins during chronic inflammation and infection. Tissues were taken from patients undergoing total knee arthroplasty (TKA) and total knee revision (TKR) procedures across two tissue depths to understand which proteins are contributing most to the dysregulation observed at the joint. Notably, p-c-Jun, p-CREB, p-BAD, IL-10, IL-12p70, IL-13, and IFN-γ contributed highly to the network of proteins involved in aseptic inflammation caused by implants. Similarly, p-PTEN, IL-4, IL-10, IL-13, IFN-γ, and TNF-α appear to be central to signaling disruptions observed in septic joints. Ultimately, the network centrality approach provided insight into the altered tissue responses observed in chronic inflammation and infection.