Inflammatory Mediator Changes During Induction and Resolution of Experimental Gingivitis

OBJECTIVES: To characterize the host biomarker response within the gingival crevicular fluid (GCF) during the induction of experimental gingivitis followed by a 4-week resolution phase.

METHODS: Experimental gingivitis was induced in 24 subjects for 21 days using intraoral stents. GCF and clinical data were collected weekly. During the resolution phase, the stents were removed at D21 and subjects were treated for 4 weeks using Sonicare-Elite toothbrushes and followed for two additional visits at days 35 and 49. Samples of GCF from Day 0, 7, 14, 21, 35 and 49 were analyzed using the Bioplex platform and R&D reagent analyte systems for 33 biomarkers including cytokines, matrix metalloproteinases (MMPs) and adipokines. Statistical testing for changes in GCF biomarker levels was performed by ANCOVA adjusting for both patient (non-stent) and baseline differences, considering p<0.05 as significant.

RESULTS: There were significant increases in gingival inflammation scores during the induction phase with a return to baseline during resolution. Compared to baseline, at Day 21 there was a significant increase in IL-1α(12-fold), IL-1β(7.8-fold) and MMP-8(2.9 fold). During induction there was also a significant decrease in many chemokines including IL-8, MIP-1β, MCP-1, ENA-78 and RANTES, the adipokine serpine-E1, as well as MMPs-1,-3 and 13. During resolution there was a significant reversal and return to baseline for all inflammatory mediators that were changed during the induction phase, except for MIP-1β which had not quite returned to baseline by day 49. No significant changes were seen in GCF levels of FGF, G-CSF, GM-CSF, IFNγ, interleukins-(2,-4,-5,-6,-10,-17 and -1ra), or TNFα, TPO, VEGF, MMP-7,9, Complement-D, CRP or Resistin.

CONCLUSIONS: Stent-induced gingivitis was associated with increases in GCF levels of IL-1α, IL-1β and MMP-8 with significant decreases in chemokines and other MMPs. The clinical and mediator changes were reversed by 4 weeks.

Work supported by Philips Oral Healthcare and RR-00046.