IL-10 Dampens an IL-17-mediated Periodontitis-associated Inflammatory Network

Objectives: We seek to delineate the inflammatory network characteristics of periodontitis and explore the modulatory biological effect of IL-10 on IL-17 mediated inflammatory responses in vitro and in vivo.
Methods: Gingival crevicular fluid (GCF) samples collected from 107 subjects were analyzed by Bio-plex multiplex for 16 inflammatory mediators. Principal component analyses (PCA) was applied to create phenotypic traits (PCTs) of those mediators. The messenger levels of cytokine genes that support Th17 differentiation were compared in periodontitis biopsies with controls in a separate population by qRT-PCR. The alveolar bone loss was compared in Il10^-/- mice to wild type (WT) controls in both Porphyromonas gingivalis oral gavage and ligature-induced periodontal bone loss models. The transcriptional levels of inflammatory genes were assessed in both murine models. The ratio of M1 /M2 macrophages isolated from Il10^-/- mice from the ligature model were compared to WT controls by FACS.
Results: PCT4, which is characterized by high positive loading of IL-17 and high negative loadings of IL-10 was significantly (p=0.004) associated with clinical periodontitis. Excessive IL-17 expression in periodontitis was also validated by significantly elevated messenger levels of IL17, IL1B and IL6 in periodontitis tissue. Il10^-/- mice presented significantly more bone loss than WT mice in both experimental alveolar bone loss models. Il17 mRNA level was elevated in Il10^-/- mice at baseline and Csf3 was significantly elevated in Il10^-/- mouse gingiva under P. gingivalis challenge (p=0.033). Il17, Ccr2 and Rank transcriptional level were also significantly increased in Il10^-/- mice in the ligature model. The ratio of M1/M2 macrophage isolated from Il10^-/- gingiva was significantly higher than that of WT mice from the ligature bone loss model.
Conclusions: IL-17 appears to be associated with an inflammatory network characteristic of periodontitis and IL-10 dampens this periodontitis-supporting IL-17 activity.