Novel host response therapeutic approaches to treat periodontal diseases

A variety of treatment strategies have been developed to target the host response to periodontal infection. This review has sought to provide mechanistic overviews and clinical applications on the use of host modulatory therapeutic regimens for periodontal disease management. Matrix metalloproteinase inhibitors, such as low-dose formulations of doxycycline, have been used in combination with scaling and root planing or surgical therapy. In addition, high-risk patient populations, such as patients with diabetes or refractory periodontal disease, have benefited from systemic matrix metalloproteinase administration. Encouraging results have been shown using soluble antagonists of tumor necrosis factor and interleukin-1 delivered locally to periodontal tissues in non-human primates, as well as more recent evidence using gene therapy vectors to provide a longer-term delivery of tumor necrosis factor receptor antagonists at the periodontium. In addition, the use of lipoxins has demonstrated significant potential in the management of the host response to periodontitis (86, 159). Other therapeutic strategies being explored are aimed at inhibiting signal transduction pathways involved in inflammation. Pharmacological inhibitors of NF-κB and p38 MAPK pathways are actively being developed to manage rheumatoid arthritis and inflammatory bone diseases (1, 95). Using this novel strategy, inflammatory mediators, including pro-inflammatory cytokines (interleukin-1, tumor necrosis factor, interleukin-6), matrix metalloproteinases and others, would be inhibited at the level of cell-signaling pathways required for transcription factor activation necessary for inflammatory gene expression or mRNA stability. These therapies may provide the next wave of disease-specific chemotherapeutics to manage chronic periodontitis. © 2007 The Authors.