Abstract
ObjectivesTo immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites.Materials and methodsA 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 established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses.ResultsMacrophages 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 with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values.ConclusionThe present immunohistochemical analysis 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 sites, which could possibly play a critical role in disease progression.Clinical relevanceMacrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host’s immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis’ underlying pathogenesis.
Highlights
Contemporary evidence has pointed macrophages as central players in immune-inflammatory processes [1, 2]
Alternative macrophages revealing a M2 phenotype are associated with anti-inflammatory reactions, including the production of IL-10 and transforming growth factor (TGF)-β to induce tissue repair and angiogenesis [1, 2, 10]
Peri-implantitis was defined as the combination of bleeding on gentle probing (BOP) with/without suppuration, probing depths (PD) ≥ 6 mm, and radiographic marginal bone loss (MBL) (i.e., “interproximal bone levels ≥ 3 mm apical of the most coronal portion of the intraosseous part of the implant”) [18]
Summary
Contemporary evidence has pointed macrophages as central players in immune-inflammatory processes [1, 2]. Clin Oral Invest (2021) 25:2335–2344 macrophages have essential functions to establish homeostasis and disease due to their phagocytic capacity and high cellular plasticity. The initiation or resolution of inflammation might be governed by macrophage phenotype alternation which is dependent on different environmental signals [8, 9]. Macrophages activated by bacteria sub-products (i.e., lipopolysaccharides) or interferon (IFN)-g present a M1 phenotype and are associated with proinflammatory responses, phagocytosis, tissue destruction, and interleukin (IL)-6 and IL-1β production. Alternative macrophages revealing a M2 phenotype are associated with anti-inflammatory reactions, including the production of IL-10 and transforming growth factor (TGF)-β to induce tissue repair and angiogenesis [1, 2, 10]
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