M1 macrophages dominate the initial phase of periodontitis and are activated by exogenous pathogen-associated and endogenous damage-associated molecular patterns, exhibiting potent phagocytosis and enhanced production of pro-inflammatory cytokines, including IL-1β, TNF-α, IL-6, IL-12 and IL-23, which clear pathogenic microorganisms while exerting pro-inflammatory effects, and remove debris and apoptotic cells [32, 36, 37]. This evidence concerns the gene TNF and periodontitis.