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Doxycycline Reduces Lipopolysaccharide‐Induced Inflammatory Mediator Secretion in Macrophage and Ex Vivo Human Whole Blood Models
Author(s) -
Cazalis Julia,
Bodet Charles,
Gag Guy,
Grenier Daniel
Publication year - 2008
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2008.080051
Subject(s) - doxycycline , aggregatibacter actinomycetemcomitans , ex vivo , tumor necrosis factor alpha , porphyromonas gingivalis , proinflammatory cytokine , lipopolysaccharide , secretion , periodontitis , macrophage , medicine , immunology , monocyte , inflammation , pharmacology , in vivo , microbiology and biotechnology , chemistry , biology , antibiotics , in vitro , biochemistry
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 <0.05) when they were pretreated with 2 μM doxycycline, whereas a concentration of 10 μM was required to significantly reduce IL‐6 secretion. Pretreatment of macrophages with 10 μM doxycycline prior to A. actinomycetemcomitans LPS stimulation resulted in a marked decrease in the phosphorylation of extracellular signal‐regulated kinase (ERK) 1/2 (−76%). In the whole blood model, doxycycline, more particularly at 10 μM, was also a potent inhibitor of the proinflammatory cytokine response. Conclusion: These two models provided clear evidence that some of the clinically proven benefits of doxycycline may be related to its ability to regulate inflammatory mediator release by host cells.