Emerging Concepts in the Resolution of Periodontal Inflammation: A Role for Resolvin E1

Abstract

Inflammatory response is a protective biological process intended to eliminate the harmful effect of the insulting influx. Resolution of inflammation constitutes an active sequence of overlapping events mediated by specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, which originate from the enzymatic conversion of polyunsaturated fatty acids (PUFAs). An unresolved acute inflammatory response results in chronic inflammation, which is a leading cause of several common pathological conditions. Periodontitis is a biofilm-induced chronic inflammatory disease, which results in loss of periodontal connective tissue and alveolar bone support around the teeth, leading to tooth exfoliation. An inadequate proresolving host response may constitute a mechanism explaining the pathogenesis of periodontal disease. An emerging body of clinical and experimental evidence has focused on the underlying molecular mechanisms of resolvins and particularly Resolvin E1 (RvE1) in periodontitis. Recently, RvE1 has been directly correlated with the resolution of inflammation in periodontal disease. Herein, we provide a comprehensive overview of the literature regarding the role and possible mechanisms of action of RvE1 on different cell populations recruited in periodontal inflammation as well as its potential therapeutic implications. Along with recent data on the benefits of PUFAs supplementation in periodontal clinical parameters, we touch upon suggested future directions for research.

Melatonin as host modulating agent supporting nonsurgical periodontal therapy in patients affected by untreated severe periodontitis: A preliminary randomized, triple‐blind, placebo‐controlled study

“…However these therapies are not easy to handle, full of side effects and interactions with other drugs . More recently resolvins have been investigated in literature: ω‐3 fatty acid as adjunct to periodontal treatment provided promising results in resolving inflammation …”

“…10 More recently resolvins have been investigated in literature: ω-3 fatty acid as adjunct to periodontal treatment provided promising results in resolving inflammation. 11 Melatonin by virtue of its effects, could be used as a novel nonpharmacological support to modulate host response in patients affected by chronic periodontitis. According to Italian Ministry of Health (24 June 2013 circular "Revaluation of the permitted intake of melatonin in food supplements") dosages of melatonin up to 1 mg are considered as dietary supplement.…”

Therapeutic potentials and modulatory mechanisms of fatty acids in bone

“…Investigations in animal models from different groups such as Bendyk et al 34 and Azuma et al 35,36 come to conclusions that tissue levels of ω-3 LCPUFAs is inversely associated with periodontic alveolar bone loss, 34 and ω-3 LCPUFAs EPA metabolite RvE1 is also established to enhance bone formation and reduce bone resorption in rabbit periodontitis models. 37 As for the anti-inflammatory effects, LCMUFAs oleic acid (OA) exhibits anti-inflammatory potentials to decrease alveolar bone loss, while LCSFAs PA shows contrary effects with elevated tumour necrosis factor α (TNF-α) levels in obesity mice models, 38 suggesting that the anti-inflammatory potentials of fatty acids in periodontitis might be varied based on specific fatty acids types. In human subjects, increased concentrations of specific SCFAs (lactic acid, propionic acid, butyric acid, isovaleric acid) have been found in the gingival fluid of periodontitis patients, demonstrating a possible association between SCFAs and inflammatory alveolar bone loss.…”

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response

“…RvE1 is a trihydroxy derivative of the polyunsaturated fatty acid EPA, and is found in fish oil and sea food. RvE1 possesses a remarkable treatment effect for many inflammation-related diseases and conditions when administered via subcutaneous injection, intraperitoneal injection, intraplantar injection and intrathecal injection [11,[13][14][15][16][17]25]. In this study, we adopted intraperitoneal injection with 1 µg RvE1 [11,16] and achieved the expected results.…”

“…Resolvin E1 (RvE1) is biosynthesized from the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), and shows remarkable potency in promoting resolution of inflammation and helping to prevent progression of an acute inflammatory response into chronic inflammation [11,12]. Antiinflammatory effects of RvE1 have been previously studied and reported in many inflammationrelated diseases and in several animal models of inflammation such as diabetic nephropathy, periodontitis, asthma, sepsis and acute respiratory distress syndrome [13][14][15][16][17]. The mechanisms of RvE1 in counteracting inflammation and promoting its resolution include suppression of procytokine expression/release, inhibition of leukocyte recruitment resulting in a reduction in the amount of local and circulatory cytokines that attenuate the inflammatory responses, and induction of macrophage phagocytosis of apoptotic polymorphonuclear neutrophils [15,18].…”