Associations between Periodontitis and Systemic Inflammatory Diseases: Response to Treatment

Abstract

There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship in all subjects would be influenced by genetic, epigenetic and other subject variables, although there are clear mechanisms that link the associations. This article includes an appraisal of patents and their applications.

Anti-inflammatory Actions of Adjunctive Tetracyclines and Other Agents in Periodontitis and Associated Comorbidities

“…Periodontal tissues respond to bacterial invasion by mobilizing defense cells and releasing inflammatory cytokines such as interleukins (IL) and tumor necrosis factor alpha (TNF-α) which ultimately cause tissue destruction by stimulating the production of enzymes such as MMPs [17]. There is increasing evidence of the plausible association between PD and an increased risk of systemic diseases [18] such as diabetes mellitus (DM), atherosclerotic cardiovascular disease (ACVD), rheumatoid arthritis (RA) and adverse pregnancy outcomes. This article reviews their clinical and biological inter-relationship with these links; and treatment responses following therapeutic approaches with tetracyclines and other anti-inflammatory agents.…”

“…It is evident that inflammatory loading from PD could give rise to multifaceted complications of CHD and DM in a systemically compromised individual [18]. High levels of glucose and fatty acids, not only lead to the production of reactive oxygen species (ROS), but the interaction between glucose and plasma proteins would result in the formation of advanced glycemic end products (AGE).…”

“…These actions could have implications on atherosclerosis and CHD [18]. In the hyperglycemic state, the interaction between glucose and structural proteins leads to non-enzymatic glycosylation, producing advanced glycation end products (AGE).…”

Does Treatment of Periodontal Disease Influence Systemic Disease?

“…Inflammatory mediators, such as TNF-a, and levels of P gingivalis are known to aggravate or partially cause the disease. [108][109][110] The presence of periodontitis is also shown to hamper RA treatment with TNF-a blockers. 111 The periodontal bacterium P gingivalis is unique among the oral flora because it possesses an enzyme needed for protein citrullination, a major hallmark of RA.…”

“…111 The periodontal bacterium P gingivalis is unique among the oral flora because it possesses an enzyme needed for protein citrullination, a major hallmark of RA. 109 Therefore, it would follow logically that reduction of the P gingivalis level and inflammation levels via periodontal treatment should decrease the severity of RA.…”