Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide

Objective - In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation. Methods and Results - LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages ( RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol ( baseline versus after treatment, 1.30 +/- 0.19 versus 1.48 +/- 0.28 mmol/L; P = 0.002) and HDL/LDL ratio (0.31 +/- 0.01 versus 0.34 +/- 0.10; P = 0.048), but lower serum LPS concentration (1.70 +/- 0.49 versus 0.98 +/- 0.50 ng/mL; P = 0.004) and autoantibodies to beta(2)-glycoprotein I (0.11 +/- 0.06 versus 0.09 +/- 0.04 ELISA units; P = 0.022) after treatment. Conclusions - Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.