Figure 2.

The ‘Two-Hit’ model of periodontal disease and its systemic implications. The ‘1st Hit’ represents local gingival inflammation induced by the subgingival biofilm. The inflammatory mediators generated by this ‘Hit’ reach the liver via the circulation to induce an acute-phase response and systemic inflammation. These circulating mediators [e.g. C-reactive protein (CRP) and interleukin-6 (IL-6)] then target other organs (e.g. the heart, to promote cardiovascular disease), including the already-inflamed gingiva, thus exacerbating periodontal disease severity (the ‘2nd Hit’). LPS, lipopolysaccharide. Modified from Golub et al.⁵³