Doxycycline Reduces Lipopolysaccharide‐Induced Inflammatory Mediator Secretion in Macrophage and Ex Vivo Human Whole Blood Models

• Published in: Journal of periodontology (1970) 2008-09, Vol.79 (9), p.1762-1768
• Main Authors: Cazalis, Julia, Bodet, Charles, Gagnon, Guy, Grenier, Daniel
• Format: Article
• Language: English
• Subjects: Adult; Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cytokine; Dentistry; doxycycline; Doxycycline - pharmacology; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Humans; Inflammation Mediators - analysis; Inflammation Mediators - blood; Interleukin-1beta - blood; Interleukin-1beta - drug effects; Interleukin-6 - analysis; Interleukin-6 - blood; Interleukin-8 - blood; Interleukin-8 - drug effects; lipopolysaccharide; Lipopolysaccharides - pharmacology; macrophage; Macrophages - drug effects; Male; Medical sciences; Middle Aged; Mitogen-Activated Protein Kinase 1 - drug effects; Mitogen-Activated Protein Kinase 3 - drug effects; Mitogen-Activated Protein Kinase 9 - drug effects; Non tumoral diseases; Otorhinolaryngology. Stomatology; p38 Mitogen-Activated Protein Kinases - drug effects; periodontitis; Periodontitis - blood; Periodontitis - microbiology; Pharmacology. Drug treatments; Phosphorylation; Porphyromonas gingivalis; Proto-Oncogene Proteins c-akt - drug effects; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - drug effects; whole blood
• ISSN: 0022-3492; 1943-3670
• DOI: 10.1902/jop.2008.080051

Background: Tetracyclines have been extensively used as adjuncts in the treatment of some forms of periodontitis. The aim of this study was to evaluate the capacity of doxycycline to influence the secretion of inflammatory mediators in macrophage and ex vivo human whole blood models stimulated with periodontopathogen lipopolysaccharides (LPS). Methods: Monocyte‐derived macrophages were treated with various concentrations of doxycycline prior to being stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) LPS. The capacity of doxycycline to mediate the inflammatory response was also tested in an ex vivo whole blood model (whole blood isolated from periodontitis patients and healthy subjects) stimulated with Porphyromonas gingivalis LPS. The secretion of interleukin (IL)‐1β, −6, and −8 and tumor necrosis factor‐alpha (TNF‐α) in both models was assessed by enzyme‐linked immunosorbent assays (ELISA). Changes in phosphorylation state of kinases induced by A. actinomycetemcomitans LPS and doxycycline in the macrophage model were characterized by a multiplex ELISA analysis. Results: The secretion of IL‐1β and −8 and TNF‐α by macrophages decreased significantly (P