Periodontal Inflammation and Systemic Diseases: An Overview

Abstract

Periodontitis is a common inflammatory disease of infectious origins that often evolves into a chronic condition. Aside from its importance as a stomatologic ailment, chronic periodontitis has gained relevance since it has been shown that it can develop into a systemic condition characterized by unresolved hyper-inflammation, disruption of the innate and adaptive immune system, dysbiosis of the oral, gut and other location's microbiota and other system-wide alterations that may cause, coexist or aggravate other health issues associated to elevated morbi-mortality. The relationships between the infectious, immune, inflammatory, and systemic features of periodontitis and its many related diseases are far from being fully understood and are indeed still debated. However, to date, a large body of evidence on the different biological, clinical, and policy-enabling sources of information, is available. The aim of the present work is to summarize many of these sources of information and contextualize them under a systemic inflammation framework that may set the basis to an integral vision, useful for basic, clinical, and therapeutic goals.

Keywords: chronic inflammation; cytokines; molecular mechanisms; oral pathogens; periodontitis; systemic diseases; systemic inflammation.

Figure 1

An overview of the pathogenesis of periodontitis. The acute inflammatory process is started by the infiltration of leukocytes (a), which limit bacterial invasion of (A) homeostatic state to (B) perturbed state (of healthy conditions to gingivitis stage). The pro-resolution mediators downregulate the recruitment of immune cells and uptake of apoptotic neutrophils by macrophages to facilitate clearance of the inflammatory lesion (Adequate balance host defense). Periodontitis is characterized by both (C) dysbiosis of oral microbiota and persistent pro-inflammatory state derived from the inability to clear the infection (b), followed by unresolved lesion leading to immune cell-mediated self-destruction of periodontal tissues which results in chronic pathology (Inadequate balance host defense). ROS, Reactive oxygen species [Figure generated with BioRender (Biorender.com)].

Figure 2

Periodontitis-associated immune and inflammatory processes. (A) Resolved inflammation and infection clearance scenario: ① Epithelial permeability and periodontopathogens entry. ② Innate immune cells detect LPS leading to pro-inflammatory cytokine production. ③ T cells are activated enhancing innate response via macrophage and neutrophil activation. ④ Macrophages and neutrophils release pro-inflammatory cytokines increasing vascular permeability. ⑤ Neutrophils clear periodontopathogens via infiltrating monocytes/macrophages, releasing tissue healing factors. ⑥ Neutrophils and macrophages exit the inflammation site and move back into the bloodstream. Pro-resolution mediators restrain immune cell influx, reversing vascular permeability, and coordinating the clearance of inflammatory debris. ⑦ The progression of acute into chronic inflammation is limited. (B) Unresolved periodontal inflammation and infection remaining scenario: ① Greater epithelial permeability and massive entry of periodontopathogens. ② Innate immune cells detect LPS, leading to pro-inflammatory cytokine production and phagocyte activation. ③ LPS activates thrombocytes, enhancing antimicrobial peptides and cytokine production. ④ Adaptive immune cells activate macrophages and neutrophils releasing pro-inflammatory cytokines. ⑤ Vascular permeability increases and leukocyte influx persist in inflamed periodontal tissues, due to failure of infection clearance, followed by the establishment of chronic inflammatory lesions. ⑥ Pro-inflammatory mediators and antimicrobial peptides are dumped into the circulation and may trigger inflammation in remote sites [Figure generated with BioRender (Biorender.com)].

Figure 3

Microbial imbalance, irregular immune response, and chronic periodontitis may exert systemic or distant effects and could lead to the activation of other disorders that share common inflammatory pathways. [Figure generated with BioRender (Biorender.com)].