Inflammatory response of Aggressive Periodontitis upon Stimulation of toll-like receptors

Background: Localized aggressive periodontitis (LAP) is a severe rapidly progressive form of periodontal disease, localized to incisors and first molars of, usually, young individuals, and can result in eventual tooth loss. The inflammatory process of the disease is attributed to recognition of bacterial components by Toll-like receptors (TLRs) in epithelial cells. Previous research has shown that a hyper-inflammatory phenotype is concomitant with LAP patients upon stimulation of TLR2 and TLR4. Objective:   To compare the inflammatory response of LAP patients with healthy siblings and controls upon stimulation of TLR 2, TLR 4, TLR1/2, TLR 5, TLR2/6. Methods: Whole peripheral blood samples were collected from a cohort of African-American adolescents aged 7-20 years. This included 9 patients diagnosed with LAP, 8 healthy siblings of LAP patients, and 7 healthy unrelated controls. Whole blood was stimulated with the appropriate ligand for each TLR and incubated for 24 hours. Unstimulated blood served as a negative control. A Luminex assay was used to measure the levels of 14 different chemo/cytokines and analyzed using Milliplex software. Kruskal-Wallis ANOVA with Dunn’s multiple comparisons were used for comparisons among experimental groups for each cytokine. Results: A hyper-response was found for LAP patients upon different TLRs, especially TLR2 stimulations for different cytokines. Overall, LAP exhibited a more robust cytokine response than either healthy control group, and healthy siblings exhibited slightly higher levels of certain cytokines than unrelated healthy controls. Conclusion: This study suggests that stimulation of different TLRs, especially TLR2, elicits a unique cytokine profile that is more robust in LAP patients. This hyper-inflammatory response is thought to contribute the severe nature of the disease.