Antibiotic-mediated immune modulation in periodontitis

Periodontitis is a chronic inflammatory disease affecting the supporting structures of the teeth. Although initiated by dysbiotic microbial communities, its progression is largely driven by the host's uncontrolled inflammatory response. While antibiotics have conventionally been employed in periodontitis therapy for their antimicrobial efficacy, emerging evidence suggests that certain antibiotics possess significant immune-modulatory properties independent of their bactericidal or bacteriostatic effects. This review explores the multifaceted immunomodulatory mechanisms by which various classes of antibiotics influence host immune cells and inflammatory pathways relevant to periodontal pathogenesis. Antibiotics were found to influence innate (e.g., pattern recognition receptors, neutrophils, macrophages, epithelial barriers, cytokine production) and acquired immunity (e.g., T and B cells). Additionally, they impact key osteoimmunology components, including interactions between immune and bone cells, the RANKL/osteoprotegerin pathway, and matrix metalloproteinase activity. Understanding the immunomodulatory actions of antibiotics enhances our understanding of their therapeutic potential in managing chronic inflammatory diseases, such as periodontitis. These properties may support inflammation resolution, immune regulation, and tissue repair, offering promising directions for future research and clinical application.