Comparison of Anti-inflammatory Effects Produced in Gingiva by Azithromycin and Metronidazole

Objectives: Previous studies suggest that azithromycin (AZM) inhibits subclinical gingival inflammation in individuals with minimal plaque. While it is unclear whether other antibiotics produce similar effects, metronidazole (MET) has been shown to decrease pro-inflammatory cytokine production by cultured periodontal ligament fibroblasts. This randomized, blinded, crossover study compared AZM and metronidazole (MET) with respect to inhibition of subclinical gingivitis.
Methods: Twelve subjects with clinically healthy gingiva and minimal plaque were randomly allocated to receive a 48 hr oral regimen of either AZM (500 mg initial dose, then 250 mg at 24 and 48 hrs) or MET (375 mg every 12 hr for 48 hr). At baseline and 2, 4, 7 and 14 days later, gingival crevicular fluid (GCF) samples were collected from twelve maxillary interproximal sites, measured, and stored frozen. After a 21 day washout, each subject received the alternative regimen. A second set of GCF samples was collected at identical time points. GCF samples were assayed for pro- and anti-inflammatory cytokine signatures by immunoassay.
Results: Both agents induced transient decreases in the rate of GCF flow on days 2, 4 and 7, followed by an increase toward baseline flow by day 14. In parallel with this effect, AZM and MET induced transient reductions in GCF IL-1β, IL-12, IL-17, G-CSF, IL-8, RANTES, VEGF and IL-4. While their effects were generally similar in magnitude, MET induced a larger decrease in GCF IL-8. Neither agent significantly altered IL-10 or IL-1 receptor antagonist.
Conclusions: In addition to their antimicrobial effects, AZM and MET reduce GCF volume and inhibit production of a similar range of pro-inflammatory cytokines and chemokines in gingiva. These anti-inflammatory effects could potentially enhance the effectiveness of these agents in treating inflammatory periodontitis.