Destructive and Protective Roles of Cytokines in Periodontitis: A Re-appraisal from Host Defense and Tissue Destruction Viewpoints

Abstract

Periodontal diseases (PD) are chronic infectious inflammatory diseases characterized by the destruction of tooth-supporting structures, being the presence of periodontopathogens required, but not sufficient, for disease development. As a general rule, host inflammatory mediators have been associated with tissue destruction, while anti-inflammatory mediators counteract and attenuate disease progression. With the discovery of several T-cell subsets bearing distinct immunoregulatory properties, this pro- vs. anti-inflammatory scenario became more complex, and a series of studies has hypothesized protective or destructive roles for Th1, Th2, Th17, and Treg subpopulations of polarized lymphocytes. Interestingly, the "protective vs. destructive" archetype is usually considered in a framework related to tissue destruction and disease progression. However, it is important to remember that periodontal diseases are infectious inflammatory conditions, and recent studies have demonstrated that cytokines (TNF-α and IFN-γ) considered harmful in the context of tissue destruction play important roles in the control of periodontal infection. Therefore, in this review, the state-of-the-art knowledge concerning the protective and destructive roles of host inflammatory immune response will be critically evaluated and discussed from the tissue destruction and control-of-infection viewpoints.

TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

“…2 As previously mentioned, it is noteworthy that the sole bacterial infection is not sufficient to explain the complex pathological processes of periodontitis, being the nature and extent of host´s response ultimately responsible for the disease occurrence and outcome. 3 While microbial and environmental factors (lifestyle factors [as smoking and stress] or acquired diseases [as diabetes]) characteristically modulate host responses (and consequently periodontitis outcome), studies suggest that as much as 50% of the risk of disease can be determined by genetic factors, [4][5][6] and that numerous disease modifying genes may be involved in the pathogenesis of periodontal diseases by modulating the host's response and his susceptibility to infection. 3,7,8 Recently, the interaction between host genetic factors that can impact the ability of pathogens to invade and proliferate on host's tissues has been termed infectogenomics.…”

“…3 While microbial and environmental factors (lifestyle factors [as smoking and stress] or acquired diseases [as diabetes]) characteristically modulate host responses (and consequently periodontitis outcome), studies suggest that as much as 50% of the risk of disease can be determined by genetic factors, [4][5][6] and that numerous disease modifying genes may be involved in the pathogenesis of periodontal diseases by modulating the host's response and his susceptibility to infection. 3,7,8 Recently, the interaction between host genetic factors that can impact the ability of pathogens to invade and proliferate on host's tissues has been termed infectogenomics. 9 This concept highlights the close and intimate dependence of the host's immune mechanisms and the commensal and/or pathogenic microflora, which co-evolved in a mutually dependent fashion.…”

Inflammatory Cytokines and the Pathogenesis of Periodontal Disease

“…Because Th1, Th2, Th17 and monocyte-derived cytokines in periodontal tissues and gingival crevicular fluid (GCF) are involved in periodontal inflammation, even a minimal imbalance of cytokine production may affect induction of bone and collagen destruction in periodontal disease [14][15][16]. As a general rule, immune responses mediated by T cells polarized into a Th1-type phenotype are characteristically cellular and pro-inflammatory; while Th2 cells are associated with humoral immunity and present anti-inflammatory properties [14].…”

“…As a general rule, immune responses mediated by T cells polarized into a Th1-type phenotype are characteristically cellular and pro-inflammatory; while Th2 cells are associated with humoral immunity and present anti-inflammatory properties [14]. IL-12, is the major cytokine which induces naive T cells in a Th1-specific manner.…”

“…As the other chronic inflammatory diseases inflammatory cytokines are considered to play an important role in the initiation, progression and the host modulation of periodontal disease [12,13] Current knowledge supports that the immunoregulatory properties of T cell derived cytokines can improve or attenuate the progression of periodontal disease [14]. There is evidence that failure to resolve inflammatory periodontal disease may be the result of an imbalance in T helper (Th) 1, Th2 and Th17 response and pro-and anti-inflammatory cytokines [14][15][16][17]. Therefore, in this mini-review, the Th cell subsets and their cytokines which are involved in the host inflammatory response and the destruction of periodontal tissues are summarized.…”