Background: Contemporary evidence has pointed macrophages as central players in immune-inflammatory processes. Macrophages have essential functions to establish homeostasis and disease due to their phagocytic capacity and high cellular plasticity. In particular, certain mechanisms like epigenetic deregulations, disruption of the periodontium/peri-implant tissue homeostasis, and a dysfunctional immunological response to bacterial endotoxins can trigger inflammatory responses at tooth and implant sites.

Aim/Hypothesis: The aim of the present study was to immunohistochemically characterize macrophage M1/M2 polarization status in human peri-implantitis lesions

Materials and Methods: A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e. bleeding on probing with or without suppuration, probing depths ≥6 mm, and radiographic marginal bone loss ≥3 mm) were included. The severity of peri-implantitis was classified according to an established criteria (i.e. slight, moderate and advanced). Soft tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment andmacrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e. CD68, CD80 and CD206) and quantified through histomorphometrical analyses.

Results: Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI: 11.4–17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI:5.9–9.4) and 5.22% (95% CI:3.8–6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI:1.12–1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared to M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values.

Conclusions and Clinical Implications: The present study suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis cases, which could possibly play a critical role in disease progression. Future research is required to understand the exact mechanisms that lead to tissue destruction and to find possible immune-modulating agents that could modulate M1/M2 status.

Acknowledgements: The work was supported by the Department of Oral Surgery and Implantology, Carolinum, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany and also by the Osteology Foundation Scholarship Grant, Lucerne, Switzerland.

Keywords: Macrophage, inflammation, peri-implantitis, macrophage polarization.