Azithromycin enhances the response to root planing and produces anti-inflammatory effects in treating chronic lung disease. This led us to hypothesize that azithromycin inhibits inflammatory mediator production in gingiva, leading to decreased gingival crevicular fluid (GCF) volume. To test this hypothesis, ten periodontally healthy volunteers received azithromycin every 24 hours for 48 hours. GCF samples were collected from 12 maxillary interproximal sites prior to azithromycin (baseline) and 2, 4, 7, and 14 days later. Samples were assayed for IL-1β, IL-8, TNF-α, VEGF, IL-6, and IL-10. With azithromycin treatment, GCF volume decreased significantly on days 2 through 7 (P < 0.05), but increased toward baseline levels on day 14. This was accompanied by a transient decrease in the content of IL-1β, IL-8, TNF-α, and VEGF (P < 0.05). IL-6 and IL-10 were not detected. Since plaque was absent throughout the study, the findings suggest that azithromycin produces anti-inflammatory effects in gingiva.
BoothVYoungSCruchleyATaichmanNSPaleologE (1998). Vascular endothelial growth factor in human periodontal disease. J Periodontal Res33:491-499.
3.
BosshardtDDLangNP (2005). The junctional epithelium: from health to disease. J Dent Res84:9-20.
4.
BurrellRCWaltersJD (2008). Distribution of systemic clarithromycin to gingiva. J Periodontol79:1712-1718.
5.
ChouCHWaltersJD (2008). Clarithromycin transport by gingival fibroblasts and epithelial cells. J Dent Res87:777-781.
6.
ChristerssonLAAlbiniBZambonJJWikesjöUMGencoRJ (1987). Tissue localization of Actinobacillus actinomycetemcomitans in human periodontitis. I. Light, immunofluorescence and electron microscopic studies. J Periodontol58:529-539.
7.
ConwayTBBeckFMWaltersJD (2000). Gingival fluid ciprofloxacin levels at healthy and inflamed human periodontal sites. J Periodontol71:1448-1452.
8.
DaranyDGBeckFMWaltersJD (1992). The relationship of gingival fluid leukocyte elastase activity to gingival fluid flow rate. J Periodontol63:743-747.
9.
DesakiMTakizawaHOhtoshiTKasamaTKobayashiKSunazukaT. (2000). Erythromycin suppresses nuclear factor-kappaB and activator protein-1 activation in human bronchial epithelial cells. Biochem Biophys Res Commun267:124-128.
Giamarellos-BourboulisEJ (2008). Macrolides beyond the conventional antimicrobials: a class of potent immunomodulators. Int J Antimicrob Agents31:12-20.
12.
GoldsteinEJCitronDMMerriamCVWarrenYTyrrellK (1999). Activities of telithromycin (HMR 3647, RU 66647) compared to those of erythromycin, azithromycin, clarithromycin, roxithromycin, and other antimicrobial agents against unusual anaerobes. Antimicrob Agents Chemother43:2801-2805.
13.
GomiKYashimaAIinoFKanazashiMNaganoTShibukawaN. (2007). Drug concentration in inflamed periodontal tissues after systemically administered azithromycin. J Periodontol78:918-923.
14.
GriffithsGS (2003). Formation, collection and significance of gingival crevice fluid. Periodontol 200031:32-42.
15.
HaasANde CastroGDMorenoTSusinCAlbandarJMOppermannRV. (2008). Azithromycin as an adjunctive treatment of aggressive periodontitis: 12-months randomized clinical trial. J Clin Periodontol35:696-704.
16.
KikuchiTHagiwaraKHondaYGomiKKobayashiTTakahashiH. (2002). Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kappa B transcription factors. J Antimicrob Chemother49:745-755.
17.
KornmanKSPageRCTonettiMS (1997). The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 200014:33-53.
LöeHSilnessJ (1963). Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand21:533-551.
20.
MascarenhasPGapskiRAl-ShammariKHillRSoehrenSFennoJC. (2005). Clinical response of azithromycin as an adjunct to non-surgical periodontal therapy in smokers. J Periodontol76:426-436.
21.
OkadaHMurakamiS (1998). Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med9:248-266.
22.
PajukantaR (1993). In vitro antimicrobial susceptibility of Porphyromonas gingivalis to azithromycin, a novel macrolide. Oral Microbiol Immunol8:325-326.
23.
PajukantaRAsikainenSSaarelaMAlaluusuaSJousimies-SomerH (1992). In vitro activity of azithromycin compared with that of erythromycin against Actinobacillus actinomycetemcomitans. Antimicrob Agents Chemother36:1241-1243.
24.
PrapullaDVSujathaPBPradeepAR (2007). Gingival crevicular fluid VEGF levels in periodontal health and disease. J Periodontol78:1783-1787.
25.
RenYHazemeijerHde HaanBQuNde VosP (2007). Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations. J Periodontol78:453-458.
26.
SchroederHEMunzel-PedrazzoliSPageR (1973). Correlated morphometric and biochemical analysis of gingival tissue in early chronic gingivitis in man. Arch Oral Biol18:899-923.
27.
ShinkaiMFosterGHRubinBK (2006). Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol290:L75-L85.
28.
SilnessJLöeH (1964). Periodontal disease in pregnancy. I. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand22:121-135.
29.
SlotsJTingM (1999). Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 200020:82-121.
30.
SmithSRFoyleDMDanielsJJoyston-BechalSSmalesFCSeftonA. (2002). A double-blind placebo-controlled trial of azithromycin as an adjunct to non-surgical treatment of periodontitis in adults: clinical results. J Clin Periodontol29:54-61.
31.
TamaokiJKadotaJTakizawaH (2004). Clinical implications of the immunomodulatory effects of macrolides. Am J Med117(Suppl 9A):5S-11S.
32.
UnluFGuneriPGHekimgilMYesilbekBBoyaciogluH (2003). Expression of vascular endothelial growth factor in human periodontal tissues: comparison of healthy and diabetic patients. J Periodontol74:181-187.
33.
van WinkelhoffAJRamsTESlotsJ (1996). Systemic antibiotic therapy in periodontics. Periodontol 200010:45-78.
34.
VanaudenaerdeBMWuytsWAGeudensNDupontLJSchoofsKSmeetsS. (2007). Macrolides inhibit IL-17-induced IL-8 and 8-isoprostane release from human airway smooth muscle cells. Am J Transplant7:76-82.
35.
ZhangJKashketSLingströmP (2002). Evidence for the early onset of gingival inflammation following short-term plaque accumulation. J Clin Periodontol29:1082-1085; erratum in J Clin Periodontol 30:278, 2003.
