Ana Cristina Andrada1, Mariane Maffei Azuma2, Hisako Furusho3, Kimito Hirai4, Shuang Xu5, Robert R White6, Hajime Sasaki7. 1. Division of Endodontics, Department of Essentials and Simulation, University of Detroit Mercy School of Dentistry, Detroit, Michigan; Division of Endodontics, Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, Massachusetts. 2. Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109. 3. Department of Oral and Maxillofacial Pathobiology, Hiroshima University, Hiroshima, Japan. 4. Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts; Department of Periodontics and Endodontics, Okayama University School of Dentistry, Kitaku, Okayama, Japan. 5. Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts; Functional Genomics Laboratory, Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 6. Division of Endodontics, Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, Massachusetts. 7. Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts. Electronic address: hajimes@umich.edu.
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 preexisting periapical lesions compared with AMP. METHODS: The susceptibility of 4 common human endodontic pathogens (Parvimonas micra, Streptococcus intermedius, Prevotella intermedia, and Fusobacterium nucleatum) to AZM, AMP, AMX, and CLI was confirmed by agar disk diffusion assay. Preexisting periapical lesions in C57BL/6J mice were treated with AZM, AMP, or phosphate-buffered saline (PBS). Periapical bone healing and the pattern of inflammatory cell infiltration were evaluated after a 10-day treatment by micro-computed tomographic and histology, respectively. Besides, the effect of antibiotics in pathogen-stimulated nuclear factor kappa B activation and the production of interleukin 1 alpha and tumor necrosis factor alpha was assessed in vitro by luciferase assay and enzyme-linked immunosorbent assay. RESULTS: All examined endodontic pathogens were susceptible to AZM, AMP, AMX, and CLI. AZM significantly attenuated periapical bone loss versus 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 nuclear factor kappa B 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 preexisting 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 preexisting periapical lesions, AZM led to advanced wound healing, probably depending on its immunomodulatory effect.
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 preexisting periapical lesions compared with AMP. METHODS: The susceptibility of 4 common human endodontic pathogens (Parvimonas micra, Streptococcus intermedius, Prevotella intermedia, and Fusobacterium nucleatum) to AZM, AMP, AMX, and CLI was confirmed by agar disk diffusion assay. Preexisting periapical lesions in C57BL/6J mice were treated with AZM, AMP, or phosphate-buffered saline (PBS). Periapical bone healing and the pattern of inflammatory cell infiltration were evaluated after a 10-day treatment by micro-computed tomographic and histology, respectively. Besides, the effect of antibiotics in pathogen-stimulated nuclear factor kappa B activation and the production of interleukin 1 alpha and tumor necrosis factor alpha was assessed in vitro by luciferase assay and enzyme-linked immunosorbent assay. RESULTS: All examined endodontic pathogens were susceptible to AZM, AMP, AMX, and CLI. AZM significantly attenuated periapical bone loss versus 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 nuclear factor kappa B 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 preexisting 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 preexisting periapical lesions, AZM led to advanced wound healing, probably depending on its immunomodulatory effect.
Authors: V Balloy; A Deveaux; D Lebeaux; O Tabary; P le Rouzic; J M Ghigo; P F Busson; P Y Boëlle; J Guez Guez; U Hahn; A Clement; M Chignard; H Corvol; M Burnet; L Guillot Journal: Br J Pharmacol Date: 2014-04 Impact factor: 8.739
Authors: Brian S Murphy; Vidya Sundareshan; Theodore J Cory; Don Hayes; Michael I Anstead; David J Feola Journal: J Antimicrob Chemother Date: 2008-01-29 Impact factor: 5.790