Local inflammatory markers and systemic endotoxin in aggressive periodontitis

Abstract

While much research has focused on local and systemic factors contributing to periodontal disease, little is known regarding mechanisms linking these factors. We have previously reported a systemic hyper-inflammatory response to bacterial endotoxin in localized aggressive periodontitis (LAP). The objectives of this study were to delineate cyto/chemokines in gingival crevicular fluid (GCF) and evaluate systemic levels of endotoxin associated with LAP. Clinical parameters, GCF, and peripheral blood were collected from: 34 LAP, 10 healthy siblings, and nine healthy unrelated control individuals. Cyto/chemokines were quantified in GCF, systemic endotoxin levels were quantified in plasma, and correlation analysis was performed among all parameters. Nine mediators were elevated in LAP diseased sites as compared with healthy sites (TNFα, INFγ, IL1β, IL2, IL6, IL10, Il12p40, GMCSF, and MIP1α, p < 0.001), while MCP1, IL4, and IL8 were elevated in healthy sites (p < 0.01). Four- to five-fold-higher endotoxin levels were detected in LAP plasma compared with that from healthy participants (p < 0.0001), which correlated with all clinical parameters and most cyto/chemokines analyzed. In conclusion, higher systemic levels of endotoxin were found in LAP, which correlates with an exacerbated local inflammatory response and clinical signs of disease. (Clinicaltrials.gov number, NCT01330719).

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.

Inflammatory mediator profile in the GCF. GCF was used for cyto/chemokine detection. D/D = LAP participant/diseased site (■), D/H = LAP participant/healthy site (▼). HS/H = healthy sibling/healthy site (○), HC/H = healthy control/healthy site (△). Dot-plots show individual participant GCF values and the median (horizontal line). Values are reported as normalized pg/mL. Any significance found was indicated by a bar on top of each graph connecting the two comparisons. *p

Figure 2.

Plasma LPS levels. Plasma was used for the detection of circulating lipopolysaccharide levels (LPS). Localized aggressive periodontitis (LAP), healthy siblings (HS), healthy unrelated control individuals (HC). *p = 0.0002, LAP vs. HS and HC (ANOVA with Dunn’s multiple comparisons).