Inflammation, Periodontal Diseases, and Systemic Health

A chronic inflammatory disease of the gingiva and periodontiumresults in destruction of gingival connective tissue, periodontal ligament, and alveolar bone. Clinically, inflammation is seen as redness, swelling, and bleeding upon probing. However, at molecular and cellular levels, the inflammatory process is defined by cellular infiltrates and the release of a variety of cytokines.1 The main provoking factor that induces inflammation of gingival tissue is the presence of bacterial biofilm (dental plaque) on the teeth/gingival interfaces.2 The products of biofilm bacteria, such as lipopolysaccharide (LPS) molecules, are known to initiate a chain of reactions in the tissue leading to host response as well as the destructive process (Figure).3

Current models of mucosal surfaces of oral, gut, lung, and skin tissue postulate that local bacterial antigens, derived from biofilms on surfaces, regulate local tolerance, local immune response, and systemic response by way of an "information relay system" through a series of nuclear factor-kappa beta pathways to synthesize and secrete cytokines and chemokines to regulate the inflammatory process at local as well as distant sites.4 Evidence is also accumulating that the predominant cells of the periodontium, gingival fibroblasts, are capable of producing prostaglandins, interleukins (IL-1beta [β], IL-6, IL-8), tumor necrosis factor-alpha (TNF-α), and interferon- gamma (IFN-γ).5 It is hypothesized that these mediators modulate inflammation locally as well as at a distant site of infection.

Is there a rationale for linking the inflammation of gingival tissue and the pathophysiology of systemic chronic inflammatory diseases? In this supplement, two mechanisms are discussed. One presupposes the direct role of oral bacteria or their products in the pathogenesis of atherosclerotic plaque in myocardial infarctions. An alternative explanation is the possible role of mediators in inflammation initiated by periodontal pathogens in the development of chronic complications.5-7 There is general agreement that chronic diseases, such as atherosclerosis, stroke, and diabetes, are multifactorial in origin. But there is growing evidence that these diseases are influenced by gingival inflammation and chronic periodontal infections. In a series of cross-sectional studies, a strong relationship has been found between acutephase C-reactive protein (CRP) in serum and the severity of periodontal diseases.8-11 CRP is triggered by infections, trauma, necrosis, and malignancy, 12 and is also linked to heart disease and diabetes. CRP is synthesized in the liver in response to proinflammatory cytokines such as IL-1α, IL-1β, and IL-6. TNF-α, IFN-γ, and transforming growth factor also participate in the production.

The current therapeutic strategy to control periodontal infections involves mechanical removal of deposits, both supra- and subgingival. This also could involve the use of topical and systemic antimicrobial agents. There are, however, very few studies to assess the effects of these therapies concomitantly with systemic health. Two pilot clinical studies with subantimicrobial administration of doxycyline indicated that these regimens reduced the "marker" of periodontal diseases, as well as risk markers of acute coronary syndrome and diabetes.12,13

Can topical antimicrobials applied via an oral delivery system (toothpaste, rinse, or gels) also achieve such an outcome? It is believed that a triclosan/copolymer/fluoride dentifrice system could provide such a benefit. Triclosan is a broad-spectrum antibacterial agent that has been shown to kill oral pathogens at 0.3 ppm to 5 ppm. Because of a favorable partition coefficient, it can readily penetrate gingival tissue and reach the target subgingivally.14 Relatively high concentrations of triclosan are retained in the plaque postbrushing (40 ppm after 2 hours and retained above minimum inhibitory concentration 12 hours postbrushing). It is an unusual antibacterial because it also has anti-inflammatory effects. For example, it inhibits both cyclooxygenase and lipooxygenase pathways at concentrations well below those retained in the dental plaque.15 It has also been observed that triclosan inhibits the release of prostaglandin E2 from IL- 1β–stimulated gingival fibroblasts, as well as reduces the actual production of IL-1β and IFN-γ.16 In long-term studies, topical effects of specially formulated triclosan have been shown to reduce or prevent periodontal disease in humans.17

The main provoking factor that induces inflammation of gingival tissue is the presence of bacterial biofilm (dental plaque) on the teeth/gingival interfaces.

Recently, such a formulation was shown to significantly improve (P = .05) oral hygiene, gingival health, and periodontal status in a group of high-risk smokers for 24 months.18 Based on the success of the agent as a topical antibacterial in the mouth, albeit in a specialized formulation, it stands to reason to evaluate the agent for its effect on periodontal inflammation concomitant to its effect on systemic inflammation. To confirm this hypothesis, long-term prospective studies will be needed.

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