Tissue-level cytokines in a rodent model of chronic implant-associated infection

Systemic cytokine concentrations have been extensively studied in implant-associated infections, providing sensitive diagnostic markers. However, less is known about the relationships of tissue-level cytokines surrounding the joint. The aim of this study was to define the cytokine profiles of tissues to investigate the use of these cytokines as markers of debridement in chronic joint infection. Using a rodent model, muscle samples were obtained from rats following Kirschner wire implantation and infection with Staphylococcus aureus to determine if: (1) differences exist in cytokine concentrations with proximity to infection, and (2) localized infection-specific markers can be identified on a tissue level to potentially serve as debridement markers in the future. Samples were collected from 4 distinct locations, and the concentrations of interleukin(IL)-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, granulocyte-macrophage colony-stimulating factor, interferon-γ, and tumor necrosis factor-α were quantified in each sample, relative to the amount of tissue. Cytokine concentrations differed with proximity to the joint when implant or infection was present, and tissues at the operative knee joint showed the highest levels of most cytokines. Additionally, IL-1β, IL-4, and IL-6 showed promise, beyond diagnostics, as tissue-level indicators of infection response. Ultimately, this study illustrated that tissue-level evaluation provided insight into infection-specific response, and these markers may be useful for guiding the debridement of implant-associated infections.