Shifting the paradigm from inhibitors of inflammation to resolvers of inflammation in periodontitis

Dyke, Thomas E. Van

doi:10.1002/jper.20-0088

Cited by 54 publications

(53 citation statements)

References 29 publications

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“…Periodontitis is associated with the presence of a dysbiotic microbial community in a susceptible host (Hajishengallis et al 2020). Although bacteria are required in disease pathogenesis, patients are not equally susceptible and do not respond similarly to treatment; it is ultimately the host inflammatory response to the microbial challenge that primarily drives immune cell–mediated self-degradation of periodontal tissues resulting in eventual tooth loss (Van Dyke 2020). Nonsurgical periodontal therapy with or without antimicrobials mechanically removes etiologic dental biofilm and remains our standard of care; however, targeting only microbes does not achieve favorable outcomes in all periodontal patients (Preshaw 2018).…”

Section: Introductionmentioning

confidence: 99%

Host Modulation and Treatment of Periodontal Disease

et al. 2021

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Periodontitis is the sixth-most prevalent disease in the world and the first cause for tooth loss in adults. With focus shifted to the inflammatory/immune response in the pathogenesis of periodontitis, there is a critical need to evaluate host modulatory agents. Synthetic and biological disease-modifying antirheumatic drugs are a cornerstone for the treatment of inflammatory diseases. Recent prospective cohort studies showed that synthetic disease-modifying antirheumatic drugs improved periodontal clinical parameters following nonsurgical periodontal treatment in patients with rheumatoid arthritis. Treatment with recombinant humanized monoclonal antibodies against CD20 (rituximab) and IL-6 receptor (tocilizumab), the latter also in clinical trials for the treatment of COVID-19 pneumonia, resulted in decreased periodontal inflammation and improved periodontal status. Studies on the effect of TNF-α inhibitors in patients with periodontitis yielded inconsistent results. Recent data suggest that probiotics provide anti-inflammatory clinical benefit, as do nutritional supplements, such as n-3 fatty acids, when combined with periodontal therapy. Probiotics reduce the production of proinflammatory cytokines/chemokines by suppressing NF-κB pathways and promote the accumulation of T regulatory cells. Statins, like aspirin, have been shown to exhibit anti-inflammatory and bone-preserving actions by upregulating production of Specialized Proresolving Mediators (SPMs). Currently, there is insufficient scientific support for the topical delivery of statins or bisphosphonates as adjuncts to periodontal therapy. Here, we present a critical review of the most recent host modulatory agents applied in humans and the key immune pathways that they target. Emerging evidence from novel drug candidates, including SPMs and complement inhibitors as previously studied in animal models and currently in human clinical trials, suggests future availability of adjunctive therapeutic strategies for the management of periodontitis.

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Section: Introductionmentioning

confidence: 99%

Host Modulation and Treatment of Periodontal Disease

et al. 2021

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“…Keystone pathogens, such as P. gingivalis , are those that assert undue influence on the local microbiome, causing dysbiosis and resulting in chronic inflammation. In parallel, but not at odds with this hypothesis [ 83 ], is the notion that unresolved inflammation, especially neutrophil-mediated, is the principal driving force for pathogenesis (reviewed in [ 84 ]). This notion has received considerable attention of late, involving novel therapeutic approaches targeting neutrophil emigration and clearance through manipulation of CXCL8 [ 85 , 86 , 87 ] or applying pre-resolving mediators.…”

Section: Indirect Antimicrobial Therapiesmentioning

confidence: 99%

Selective Antimicrobial Therapies for Periodontitis: Win the “Battle and the War”

Elashiry

Morandini

Timothius

et al. 2021

IJMS

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Traditional antimicrobial therapies for periodontitis (PD) have long focused on non-selective and direct approaches. Professional cleaning of the subgingival biofilm by instrumentation of dental root surfaces, known as scaling and root planning (SRP), is the mainstay of periodontal therapy and is indisputably effective. Non-physical approaches used as adjuncts to SRP, such as chemical and biological agents, will be the focus of this review. In this regard, traditional agents such as oral antiseptics and antibiotics, delivered either locally or systemically, were briefly reviewed as a backdrop. While generally effective in winning the “battle” against PD in the short term, by reducing its signs and symptoms, patients receiving such therapies are more susceptible to recurrence of PD. Moreover, the long-term consequences of such therapies are still in question. In particular, concern about chronic use of systemic antibiotics and their influence on the oral and gut microbiota is warranted, considering antibiotic resistance plasmids, and potential transfer between oral and non-oral microbes. In the interest of winning the “battle and the war”, new more selective and targeted antimicrobials and biologics for PD are being studied. These are principally indirect, blocking pathways involved in bacterial colonization, nutrient acquisition, inflammation or cellular invasion without directly killing the pathogens. This review will focus on current and prospective antimicrobial therapies for PD, emphasizing therapies that act indirectly on the microbiota, with clearly defined cellular and molecular targets.

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“…One area of bacterial infections that has been studied fairly extensively with SPMs is periodontitis. 24,25 Exogenous administration of SPMs has been shown in animal studies to dramatically aid in healing periapical lesions and reducing inflammation. [26][27][28][29] Periodontitis is generally caused by bacterial overgrowth, often Porphyromonas gingivalis, leading to biofilm formation and mucosal inflammation.…”

Section: Periodontitismentioning

confidence: 99%

“…One area of bacterial infections that has been studied fairly extensively with SPMs is periodontitis 24,25 . Exogenous administration of SPMs has been shown in animal studies to dramatically aid in healing periapical lesions and reducing inflammation 26–29 .…”

Section: Spms In Bacterial Infectionsmentioning

confidence: 99%

Specialized proresolving mediators in infection and lung injury

Sandhaus

Swick

2020

BioFactors

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Specialized proresolving mediators (SPMs) are endogenous lipid metabolites of long-chain polyunsaturated fatty acids that are involved in promoting the resolution of inflammation. Many disease conditions characterized by excessive inflammation have impaired or altered SPM biosynthesis, which may lead to chronic, unresolved inflammation. Exogenous administration of SPMs in infectious conditions has been shown to be effective at improving infection clearance and survival in preclinical models. SPMs have also shown tremendous promise in the context of inflammatory lung conditions, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease, mostly in preclinical settings. To date, SPMs have not been studied in the context of the novel Coronavirus, severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), however their preclinical efficacy in combatting infections and improving acute respiratory distress suggest they may be a valuable resource in the fight against Coronavirus disease-19 (COVID-19). Overall, while the research on SPMs is still evolving, they may offer a novel therapeutic option for inflammatory conditions.

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Shifting the paradigm from inhibitors of inflammation to resolvers of inflammation in periodontitis

Cited by 54 publications

References 29 publications

Host Modulation and Treatment of Periodontal Disease

Host Modulation and Treatment of Periodontal Disease

Selective Antimicrobial Therapies for Periodontitis: Win the “Battle and the War”

Specialized proresolving mediators in infection and lung injury

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