Objectives: Severe periodontitis has been associated with increased systemic inflammation and pro-atherogenic lipid serum concentrations in otherwise healthy subjects. We explored whether these associations were causal in nature by investigating the impact of periodontal therapy on serum inflammatory and lipid markers. Methods: 65 healthy subjects with severe generalized periodontitis participated in a single-blind, 3 arms randomized controlled clinical trial. Medical and periodontal parameters, C-reactive protein (CRP, primary outcome variable), interleukin-6 (IL-6), total and LDL-cholesterol were evaluated prior and two months after treatment. The 3 treatment groups included an untreated control, standard periodontal therapy (SPT) consisting of machine-driven sub-gingival debridement and an intensive course of periodontal treatment (IPT= SPT and locally delivered antibiotic within 6 hrs). Results: 2 months after treatment, both treatment groups resulted in a significant mean reduction of 0.5±0.2 mg/L (95% CI 0-0.9, P=0.030, SPT) and 0.8±0.2 mg/L (95% CI 0.3-1.2, P=0.001, IPT) respectively in serum CRP compared to the untreated control. Individuals in the IPT group presented also with a greater mean reduction in IL-6 levels when compared to the control (0.5±0.2 ng/L, 95% CI 0.2-0.9, P=0.006) and to the SPT group (0.6±0.2 ng/L, 95% CI 0.2-1.0, P=0.002). These reductions were independent of age, gender, body mass index, ethnicity, whereas a significant interaction effect of cigarette of smoking was found. Both reduction in CRP and IL-6 were significant only in non smoker individuals (P=0.028 and P=0.003 univariate tests respectively) while in current smokers only IPT group showed a significant effect on inflammatory markers. The IPT group further showed a decrease in total cholesterol and LDL-cholesterol concentrations after two months. Conclusions: These data indicate that periodontitis causes moderate systemic inflammation in systemically healthy subjects. An intensive treatment approach including a locally delivered antibiotic produced greater reductions in serum inflammatory markers when compared to the standard treatment regimen.

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