Effect of adjunctive roxithromycin therapy on interleukin-1β, transforming growth factor-β1 and vascular endothelial growth factor in gingival crevicular fluid of cyclosporine A-treated patients with gingival overgrowth.
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)-1β, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) levels in gingival crevicular fluid of renal transplant patients.


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-1β, TGF-β1 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-1β, TGF-β1 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-1β, TGF-β1 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-1β and VEGF between the two study groups. The amount of decrease in TGF-β1 levels for the ROX group was statistically significant compared to that for the placebo group at 4 wk after treatment (p < 0.017).


CONCLUSIONS
Our study indicated that combination of ROX with non-surgical therapy improves gingival overgrowth status and decreases gingival crevicular fluid TGF-β1 levels in patients with severe gingival overgrowth. The reduction of gingival crevicular fluid TGF-β1 following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of ROX on the treatment of cyclosporine A-induced gingival overgrowth.
Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, China.
Y
Y
Gong
J
J
Lu
X
X
Ding
Y
Y
Yu
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000009:adverse effects*; D003774:Dental Plaque Index; D012534:Dental Scaling / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005883:Gingival Crevicular Fluid / Q000187:drug effects* / Q000276:immunology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D053583:Interleukin-1beta / Q000187:drug effects*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010512:Periodontal Index; D010514:Periodontal Pocket / Q000145:classification / Q000628:therapy; D010919:Placebos; D016745:Root Planing / Q000379:methods; D015575:Roxithromycin / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D010919:Placebos; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015575:Roxithromycin; D016572:Cyclosporine
cyclosporine A; gingival overgrowth; interleukin-1β; periodontal therapy; roxithromycin; transforming growth factor-β1; vascular endothelial growth factor