TNF and periodontitis: During the progression of periodontitis, on one hand, periodontal pathogens may induce an excessive inflammatory response by modulating metabolic pathways to skew macrophage polarization towards M1, while on the other hand, sites of alveolar bone destruction accumulate large numbers of M1 macrophages, leading to the production of IL-1β and TNF-α, upregulation of RANKL expression, and increased bone resorption (113, 114).