MACROLIDE ANTIBIOTICS LIKE AZITHROMYCIN INCREASE LIPOPOLYSACCHARIDE-INDUCED IL-8 PRODUCTION BY HUMAN GINGIVAL FIBROBLASTS

Objective: Macrolide antibiotics are reported to modulate the production of cytokines in various type of cells. We examined the effect of macrolide antibiotics on inflammatory cytokines (IL-6 and IL-8) and chemical mediator (PGE(2)) and also matrix metalloproteinases (MMPs) productions by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS). Methods: The effect of macrolide antibiotics [erythromycin (EM), azithromycin (AZM) and josamycin (JOM)] on HGFs proliferation were examined by MTT assay. HGFs were treated with LPS from Porphyromonas gingivalis (PgLPS) and macrolide antibiotics, and IL-6, IL-8 and PGE(2) levels were evaluated by ELISA. MMPs were detected by gelatin zymography. Results: AZM slightly but significantly decreased HGFs proliferation, while EM and JOM did not affected. AZM increased PgLPS-induced IL-8 production dose-dependently, while AZM did not alter IL-6 and PGE(2) productions. EM and JOM did not altered PgLPS-induced IL-6, IL-8 and PGE2 productions. All macrolide antibiotics did not alter MMPs production. These results indicate that macrolide antibiotics have no direct anti-inflammatory effect. However, the use of the inhibitors of cell signaling pathway failed to reveal the mechanism that AZM enhanced PgLPS-induced IL-8 production. Conclusion: These results Suggest macrolide antibiotics have an indirect anti-inflammatory effect as a result of their antimicrobial properties. Because AZM increased I-PS-induced IL-8 production by HGFs, the possibility is considered that neutrophils may be migrated to periodontal tissue and phagocytize the periodontopathic bacteria more efficiently