Local inflammatory markers and systemic endotoxin in aggressive periodontitis.

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, IL1ß, 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).

Hyper-responsive phenotype in localized aggressive periodontitis.

The 'hyper-responsive' trait is an increased inflammatory response upon stimulation of innate immune receptors. Our objective was to determine if a hyper-reactive trait is present in a cohort diagnosed with aggressive periodontitis (LAgP). Peripheral blood was collected from 30 LAgP, 10 healthy unrelated, and 10 healthy sibling participants and stimulated with lipopolysaccharide (LPS) from E. coli and P. gingivalis. Cyto/chemokine response profiles were evaluated and analyzed by ANOVA. Elevated levels of pro-inflammatory cyto/chemokines were detected in E. coli and P. gingivalis LPS-stimulated LAgP cultures when compared with those of healthy unrelated control individuals. Periodontally healthy siblings presented with attenuated hyper-inflammatory cyto/chemokine profiles. Regression analysis demonstrated the hyper-reactive trait to be concomitant expression of pro-inflammatory cyto/chemokines and an absence of anti-inflammatory mediator expression. Our findings demonstrate hyper-responsive trait in a LAgP cohort, along with an attenuated hyper-responsiveness in healthy siblings, which can be induced in response to multiple TLR ligations.

Spinal neurons activated in response to pudendal or pelvic nerve stimulation in female rats.

The overlapping distribution of spinal neurons activated with either pudendal sensory nerve or pelvic nerve stimulation was examined in the female rat using c-fos immunohistochemistry. Pudendal sensory nerve stimulation resulted in a significant increase in fos-positive cells in the ipsilateral dorsal horn and bilaterally in the medial, lateral and intermediate gray of L5-S1. Pelvic nerve stimulation resulted in significant increases of c-fos immunoreactive nuclei in the ipsilateral dorsal horn, lateral and intermediate gray and bilaterally in the medial gray of L5-S1. Co-distribution of fos immunoreactive nuclei with the vesicular glutamate transporters (VGlut2 and VGlut3) and neurokinin I receptors were found in distinct regions of the dorsal horn, medial and lateral gray. Specific areas in the medial dorsal horn, dorsal gray commissure, laminae VI and X and dorsal lateral gray were activated after stimulation of the pudendal sensory and pelvic nerves, suggesting these areas contain spinal neurons that receive both somatomotor and visceral inputs and are part of the intraspinal circuit that regulates sexual and voiding function.