Systemic IFNγ predicts local implant macrophage response

Implantation of biomaterials can cause complica- tions often associated with inflammatory reactions. However, repeated evaluation of the implant site would be burdening for patients. Alternatively, blood examinations with analysis of inflammatory serum markers could potentially be useful to reflect the local cellular response for detection and/or prediction of inflammation-related complications. Therefore, following intramuscular implantation of surface-modified Ti implants in rats, this study aimed at examining possible associations between the post-implantation time course of pro-inflammatory (INFc, IL-2) and anti-inflammatory (IL-4, IL-10) cytokine serum concentrations and the local peri-implant tissue response after 56 days (pro-inflammatory CD68-positive monocytes/ macrophages, anti-inflammatory CD163-positive macro- phages, MHC class II-positive cells, activated natural killer cells and mast cells). Multivariate correlation analysis revealed a significant interaction between serum IFNc and peri-implant tissue CD68-positive monocytes/macrophages (p = 0.001) while no interactions were found for other cytokines and cell types. Additional Pearson correlation analysis of IFNc serum concentrations on each experimental day vs. the CD68-positive monocytes/macrophages response on day 56 demonstrated a consistently positive correlation that was strongest during the first three weeks. Thus, high early pro-inflammatory IFNc serum concentration was associated with high late number of pro-inflammatory CD68-positive monocyte/macrophages and low early serum IFNc with low late CD68-positive mono- cyte/macrophage numbers. Further studies aimed at examina- tion of patient samples could establish the relevance of this association to predict clinical complications. Graphical Abstract After implantation of titanium sam- ples, high early IFNc serum concentrations were associated with a pronounced late pro-inflammatory CD68-positive monocyte/ macrophage (red circle) response, while no correlation was found for other investigated cytokines and inflammatory cells (green circle). In contrast, low early IFNc serum concentrations were correlated with low late monocyte/ macrophage numbers.