Effect of adjunctive roxithromycin therapy on interleukin-1beta, transforming growth factor-beta1 and vascular endothelial growth factor in gingival crevicular fluid of cyclosporine A-treated patients with gingival overgrowth.

BACKGROUND AND OBJECTIVE: Systemic macrolide antibiotic administration has been shown to result in the elimination or reduction cyclosporine A-induced gingival overgrowth. Roxithromycin (ROX) is known to have anti-inflammatory, immunomodulatory and tissue reparative effects. This study was to evaluate the effect of adjunctive ROX therapy on cyclosporine A-induced gingival overgrowth and interleukin (IL)-1beta, transforming growth factor (TGF)-beta1 and vascular endothelial growth factor (VEGF) levels in gingival crevicular fluid of renal transplant patients. MATERIAL AND METHODS: Thirty-one patients with clinically significant overgrowth and 16 periodontally healthy subjects were included in this randomized, double-blind, placebo-controlled, parallel-arm study. Patients received scaling and root planing (SRP) at baseline and randomized to take either ROX or placebo for 5 d. The clinical parameters, including plaque index, papillary bleeding index, probing depth and gingival overgrowth scores, were recorded. The amounts of IL-1beta, TGF-beta1 and VEGF in gingival crevicular fluid were detected by ELISA. Periodontal parameters as well as gingival crevicular fluid biomarker levels were evaluated at baseline and at 1 and 4 wk post-therapy. RESULTS: Following SRP plus ROX and SRP plus placebo therapy, significant improvements in clinical periodontal parameters of both study groups were observed (p < 0.025). In the ROX group, adjunctive ROX therapy resulted in a greater gingival overgrowth scores reduction compared with those in the placebo group at 4 wk (p < 0.017). Initial amounts of IL-1beta, TGF-beta1 and VEGF for both the ROX and placebo groups were significantly higher than those for healthy subjects (p < 0.017), with no statistical difference between the two study groups. At 1 and 4 wk post-therapy, significant decreases in the amounts of IL-1beta, TGF-beta1 and VEGF were observed in both study groups when compared with baseline (p < 0.025), but there was no difference in the levels of IL-1beta and VEGF between the two study groups. The amount of decrease in TGF-beta1 levels for the ROX group was statistically significant compared to that for the placebo group at 4 wk after treatment (p < 0.017). CONCLUSION: Our study indicated that combination of ROX with non-surgical therapy improves gingival overgrowth status and decreases gingival crevicular fluid TGF-beta1 levels in patients with severe gingival overgrowth. The reduction of gingival crevicular fluid TGF-beta1 following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of ROX on the treatment of cyclosporine A-induced gingival overgrowth.