Specialized Pro-resolving Mediators: Resolving Inflammation and Restoring Bone

Abstract

Periodontitis is a chronic inflammatory disease characterized by gingival inflammation and loss of periodontal ligament attachment, which if severe enough can lead to the irreversible destruction of surrounding alveolar bone. In chronic inflammation, hosts are in a prolonged state of dysbiosis characterized by more proinflammatory cells and cytokines. This results in a lack of their anti-inflammatory counterparts, stopping the ability of the host periodontium from resolving naturally. Under normal circumstances, inflammation is resolved, and the immune system is returned to baseline through the action of endogenous lipid-derived molecules called specialized pro-resolving mediators (SPMs). Specialized pro-resolving mediators (SPMs) are an endogenous class of fatty acid-derived molecules that function to return the immune system to homeostasis. Recent pre-clinical studies showed that administered SPMs successfully resolved inflammation in rabbit and swine models of periodontitis. Phase I clinical trials using the lipoxin class of SPM in a mouth rinse demonstrated that SPMs were well tolerated by patients, and post-hoc efficacy analyses indicated that SPM therapy reduced gingival inflammation. Evidence also suggests that lipoxin administration reduced bleeding on probing and pocket depth in a subset of patients with advanced periodontitis. These studies collectively indicate that SPMs restore alveolar bone and regenerate periodontal ligament (PDL). This article will review the recent evidence demonstrating that SPM therapy resolves inflammation by inhibiting neutrophil chemotaxis and proinflammatory cytokine secretion. SPMs reduce bone resorption, restore alveolar bone, and regenerate PDL. Although further clinical studies are needed to evaluate the best SPM class and dosage, these data indicate that SPM therapy has the potential to transform the treatment of periodontitis.