Effects of Smoking on Macrophage Polarization in Peri-Implantitis Lesions

Abstract

Objectives: The study aimed to investigate the relationship between cigarette smoking and macrophage polarization in peri-implantitis (PI) lesions. Additionally, it sought to characterize clinical, radiological, microbiological, and immunological features of PI in smokers and non-smokers.

Materials and methods: A cross-sectional study included 40 patients (20 smokers, ≥ 10 cigarettes/day, and 20 non-smokers) requiring surgical treatment for PI. Samples of peri-implant crevicular fluid (PICF) and granulation tissue were collected during surgery for immunofluorescence and cytokine analyses. Smoking exposure was assessed through cotinine levels. Macrophage polarization (M1/M2) was determined using immunofluorescence. Clinical, radiological, and microbiological parameters were also evaluated.

Results: Smokers showed a significantly higher proportion of M1 macrophages (70.23%) compared to non-smokers (25.09%, p < 0.005). This pro-inflammatory shift correlated positively with cotinine levels (ρ = 0.694; p < 0.005) and pack-years (ρ = 0.81; p < 0.005). No significant differences in M2 macrophage counts, cytokine concentrations, or microbiota diversity were observed between the groups. However, smokers exhibited more severe PI lesions (p = 0.04).

Conclusions: Smoking is associated with a pro-inflammatory shift at the cellular level due to an increase in M1 macrophage polarization in PI lesions, suggesting a pro-inflammatory response that may exacerbate tissue destruction and hinder treatment outcomes. These findings highlight the need for incorporating smoking cessation into comprehensive peri-implant care strategies to improve disease management and implant prognosis.

Keywords: dental implants; macrophage polarization; peri‐implantitis; smoking.

FIGURE 1

Immunofluorescence analysis showing CD68 (green, FITC), iNOS (orange, Alexa 561), and CD206 (red, PercP). M1 macrophages appear yellow‐green due to co‐localization of CD68 and iNOS, while M2 macrophages appear orange‐red indicating CD206 expression. Representative images demonstrate a higher prevalence of M1 macrophages in smokers.

FIGURE 2

Box plots depicting macrophage quantification across samples: (A) Total number of macrophages per μm², (B) Number of M1 macrophages per μm², (C) Number of M2 macrophages per μm², and (D) Proportion of M1 macrophages relative to the total macrophage population.