Macrophage Phenotype Alterations in Treated Periodontitis Patients Suggest a Pro-Inflammatory Bias

Understanding macrophage polarization in periodontitis is critical for elucidating the underlying disease mechanisms. This exploratory study aimed to characterize phenotypic features of monocyte-derived macrophages (MDMs) from treated periodontitis patients.

Peripheral blood mononuclear cells were isolated from 30 individuals classified into three groups: periodontal healthy (H) and patients with treated stage III, grade B (PIII-B) or grade C (PIII-C) periodontitis. Monocytes were differentiated into macrophages and cultured under non-polarizing (M0), M1-polarizing (LPS + IFN-γ), or M2-polarizing (IL-4 + IL-13) conditions. MDM polarization was evaluated by immunophenotyping and cytokine secretion profiling.

Under M0 conditions, the percentage of M1 MDMs decreased in the H group but remained stable in both periodontitis groups, particularly in PIII-C, which exhibited a higher M1/M2 ratio. Following M1 stimulation, no significant differences in M1/M2 ratios were observed among groups. However, H MDMs increased VEGF and IL-10 secretion compared with those from PIII-B. Under M2 stimulation, PIII-C MDMs exhibited a higher proportion of M1 cells and increased IL-6 secretion, while PIII-B MDMs demonstrated an elevated M1/M2 ratio and lower IL-10 response, suggesting a shift toward a more pro-inflammatory profile.

In this exploratory study, MDMs from individuals with successfully treated stage III, grade B or C periodontitis exhibited a tendency toward a M1-like phenotype across different polarization conditions, indicating the possible persistence of a pro-inflammatory immune trait that requires confirmation in longitudinal and mechanistic studies.