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Inflammatory Suppression: Rationale and Implications for the General Practice

During the past few years, the literature has been strongly supportive of a distinct link between oral disease, mainly periodontitis, and a host of systemic entities. It has become more and more apparent that the relationship is related to the inflammatory response. The host immune mechanism, which is both a local and a systemic phenomenon, is an integral part of the puzzle, inasmuch as it is so intimately a part of the inflammatory process.
The contemporary and constantly evolving standard of care now dictates that the general dentist be an integral part of the recognition and control of the oral inflammatory pathoses. As healthcare providers, we share the responsibility for our patients’ general medical health.1 The most ubiquitous conditions within our purview, with the greatest incidence, are the periodontal diseases. This article will review the development of the inflammatory response in the periodontal patient, discuss its relationship to systemic disease, and outline the dentist’s role in recognition and management.

Figure 1. Pathologic inflammatory reaction.

Figure 2. Type III periodontitis in diabetic with poor glycemic control.

Figure 3. Lateral border of tongue.

Figure 4. Fluorescence with ViziLite (Zila Pharmaceuticals).

Figure 5. Retention of toluidine blue, later diagnosed through biopsy as severe dysplasia.


To date, there are more than 700 species of organisms identified as being cultivable from the oral cavity,2 and of these, at least 30 have pathogenic potential and play a role in the periodontal diseases.3 The role of bacteria in the periodontal infectious process has been well described, and it is still being unraveled. Periodontitis in its various forms can be described as “a form of aberrant inflammation” resulting from a highly complex biofilm of both pathogenic and nonpathogenic (commensal) organisms which initiate the host inflammatory response.4
Table 1.
"The red cluster" of critical periodontal pathogens
Porphyrmonas gingivalis Aggregatibacter actinomycetimcomitans
Tanerella forsythensis Treponema denticola

The gram negative periodontopathogens, especially those in the “red cluster or complex” (Table 1),5 appear to have the capacity to initiate the production of a number of inflammatory mediators, such as cytokines,6,7 in addition to their direct invasive, destructive roles. The primary goal of early intervention in periodontal anti-infective therapy is to reduce the bacterial load, and thus limit the inflammatory response of the immune system. Removal of the subgingival biofilm by instrumentation can remove up to 90% of the microbial deposits on the root surface.8
There are a number of mechanisms that constitute part of the host immune response that either protect the tissues or initiate and promote destruction. This variability of the responses is an important factor in how the periodontal diseases are expressed in the population.9,10 It is the immunopathologic aspect of the immune response that creates the inflammatory response and the subsequent destruction (Figure 1). There are numerous contributory risk factors that may affect the nature and intensity of the immune response, in addition to host variability. These factors that modify the host response contribute to the systemic nature of the inflammation. For example, smoking has been shown to impair polymorphonuclear leukocyte function and promote the production of proinflammatory cytokines.11,12 Table 2 lists some, but not all, of the many risk factors that influence the nature of the inflammatory response in contributing to the onset of periodontal pathosis and its sequelae.
The immune response, resulting in inflammation and tissue destruction, is a complex interaction of cellular events resulting in the release of metabolites that result in destruction of the collagen supporting the connective tissue, and eventually supporting alveolar bone. The highly cellular local response revolves around the chemotactic response of leukocytes, the influx of B and T lymphocytes, macrophages, and the presence of fibroblasts, all of which contribute to the admix of cytokines, leukotrienes, and other destructive metabolites.13,14 The resulting inflammatory response is far from purely a localized phenomenon. While periodontal disease is, indeed, often a site-specific phenomenon, the mediators or metabolites produced are disseminated systemically. This is the critical rationale for suppression or reduction of the immune inflammatory response of periodontal disease.

Table 2.
Genetics Oral Hygiene Pregnancy
Age Gender Puberty
Medications Smoking Blood dyscrasias
Metabolic disorders Iatrogenic factor Autoimmune disease

Table 3.
Systemic conditions with evidence linked to periodontal inflammation
Cardiovascular disease16
Pulmonary Disease32
Chronic Obstructive Pulmonary disease27
Ischemic stroke20
Preterm births17 Alzheimer’s disease30
Eclampsia29 Osteoporosis28
Atherosclerosis21 Oral and pancreatic cancer33-35
Diabetes18,24 Nosocomial bacterial pneumonia27
Kidney and renal dysfunction31  


The literature is replete with references to significant associations of periodontal disease to other body systems, a few of which are referenced here.15-20 The dissemination of the inflammatory response has many ramifications, with regard to the evolving systemic links in the literature. Some of the many diseases and inflammatory related pathoses are listed in Table 3. Perhaps the most cited systemic associations in the current literature are in relation to coronary heart disease as a possible sequela of periodontal inflammation, as implicated in the identification of Porphyrmonas gingivalis DNA in atheromatous plaque21, innumerable other citations associating periodontitis with increased prevalence for CHD (chronic heart disease)22, and elevated levels of anticardiolipin antibodies in individuals with essential hypertension.23
The added risk of CHD in combination with diabetes makes cardiovascular disease the number one cause of mortality in diabetics.18,24 Again, it is because of the compromised immune system of the diabetic, resulting in altered inflammatory responses, that periodontitis is considered the sixth complication of diabetes.25 The diabetic with periodontal inflammation, as in Figure 2, presents with reduced glucose tolerance, increased resistance to insulin, and dramatically increased risk for all of the complications of diabetes including cardiovascular disease.
There are numerous other systemic sequelae linked to periodontal inflammation, with more links and associations being suggested almost daily in the literature.26-32 There is another relationship with inflammatory periodontal disease that, currently, is being intensively investigated. The alarming morbidity and mortality of oral/pharyngeal cancer, especially oral squamous cell carcinoma (OSCC), appears to have a definitive relationship to oral inflammation and to the human papilloma virus (HPV).32 Chronic periodontitis is associated with increased risk for cancer of the tongue33, and pancreatic cancer in men has been linked to poor oral hygiene and periodontal disease.34 It is suggested that elevated levels of nitrosamines in the gut react with digestive chemicals to create conditions that favor development of pancreatic cancer. The elevated levels of C reactive protein (CRP) are part of an early immune system response to persistent inflammation, and have been linked to the development of pancreatic cancer.35,36
The consistent thread that binds all of these observations together is the presence of inflammation, resulting from periodontal pathology. The implications for dentistry are enormous. The dental profession, armed with the ability to detect the early changes in oral tissues by using currently available technology, such as adjunctive oral cancer screen-ing techniques (eg, ViziLite [Zila Pharmaceuticals]) (Figures 3 to 5), is in a position to reverse the ominous trends in morbidity and mortality of OSCC by visualizing cellular changes before they can be seen by the unaided eye. This noninvasive test, with a 99% negative predictive value, is a major step forward in early detection.


The inflammatory component of both cancer and other systemic entities is within our control. Understanding the importance of early recognition and instituting measures for control is precisely what periodontal management is all about. Our ability to suppress the inflammatory response with instrumentation, adjunctive therapy (including host modulation), and daily disease control, puts the general practitioner and hygienist at the forefront of this enormous public health issue, and we can make a huge difference.


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Dr. Bader practices periodontics and implant dentistry in Concord, Mass. He is a graduate of NYU College of Dentistry, and in 1966 completed a residency in periodontology at the Harvard School of Dental Medicine, where he currently serves as lecturer in postgraduate periodontology. He is a fellow of the American College of Dentists, International College of Dentists, and American Academy of Osseointegration. He has been published in the Journal of Dental Research, Journal of Periodontology, Journal of Clinical Periodon-tology, and the American Journal of Dentistry. He can be reached at This email address is being protected from spambots. You need JavaScript enabled to view it..

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