{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:55:20Z","timestamp":1790268920944,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> 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).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Monocyte\u2010derived macrophages were treated with various concentrations of doxycycline prior to being stimulated with <jats:italic>Aggregatibacter actinomycetemcomitans<\/jats:italic> (previously <jats:italic>Actinobacillus actinomycetemcomitans<\/jats:italic>) 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 <jats:italic>Porphyromonas gingivalis<\/jats:italic> LPS. The secretion of interleukin (IL)\u20101\u03b2, \u22126, and \u22128 and tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) in both models was assessed by enzyme\u2010linked immunosorbent assays (ELISA). Changes in phosphorylation state of kinases induced by <jats:italic>A. actinomycetemcomitans<\/jats:italic> LPS and doxycycline in the macrophage model were characterized by a multiplex ELISA analysis.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The secretion of IL\u20101\u03b2 and \u22128 and TNF\u2010\u03b1 by macrophages decreased significantly (<jats:italic>P<\/jats:italic> &lt;0.05) when they were pretreated with 2 \u03bcM doxycycline, whereas a concentration of 10 \u03bcM was required to significantly reduce IL\u20106 secretion. Pretreatment of macrophages with 10 \u03bcM doxycycline prior to <jats:italic>A. actinomycetemcomitans<\/jats:italic> LPS stimulation resulted in a marked decrease in the phosphorylation of extracellular signal\u2010regulated kinase (ERK) 1\/2 (\u221276%). In the whole blood model, doxycycline, more particularly at 10 \u03bcM, was also a potent inhibitor of the proinflammatory cytokine response.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> 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.<\/jats:p>","DOI":"10.1902\/jop.2008.080051","type":"journal-article","created":{"date-parts":[[2008,9,4]],"date-time":"2008-09-04T20:03:05Z","timestamp":1220558585000},"page":"1762-1768","source":"Crossref","is-referenced-by-count":59,"title":["Doxycycline Reduces Lipopolysaccharide\u2010Induced Inflammatory Mediator Secretion in Macrophage and Ex Vivo Human Whole Blood 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