Immunomodulation mediated by azithromycin in experimental periapical inflammation

Abstract Introduction The purpose of the present study was to compare the immunomodulatory effect of azithromycin (AZM), ampicillin (AMP), amoxicillin (AMX) and clindamycin (CLI) “ in vitro ” and AZM on pre-existing periapical lesions when compared to ampicillin (AMP). Methods Susceptibility of four common human endodontic pathogens (Parvimonas micra, Streptococcus intermedius, Prevotella intermedia, and Fusobacterium nucleatum) to AZM, AMP, AMX, and CLI was confirmed by agar disc diffusion assay. Pre-existing periapical lesions in C57BL/6J mice were treated with AZM, AMP, or PBS (phosphate buffered saline). Periapical bone healing and pattern of inflammatory cell infiltration were evaluated after a 10-day treatment by micro computed tomography and histology, respectively. Besides, the effect of antibiotics in pathogen-stimulated NF-κB activation and production of IL-1α and TNF-α was assessed in vitro by luciferase assay and ELISA. Results All examined endodontic pathogens were susceptible to AZM, AMP, AMX, and CLI . AZM significantly attenuated periapical bone loss vs. PBS. PBS resulted in widely diffused infiltration of mixed inflammatory cells. By contrast, AZM brought about localized infiltration of neutrophils and M2 macrophages and advanced fibrosis. Although the effect of AMP on bone was uncertain, inflammatory cell infiltration was considerably milder than PBS. However, most macrophages observed seemed to be M1 macrophages. AZM suppressed pathogen-stimulated NF-κB activation and cytokine production, whereas AMP, AMX, and CLI reduced only cytokine production moderately. Conclusions This study showed that AZM led to the resolution of pre-existing experimental periapical inflammation. Our data provide a perspective on host response in antibiotic selection for endodontic treatment. However, well-designed clinical trials are necessary to better elucidate the benefits of AZM as an adjunctive therapy for endodontic treatment when antibiotic therapy is recommended. Although both AZM and AMP were effective on pre-existing periapical lesions, AZM led to advanced wound healing probably depending on its immunomodulatory effect.