Association study between salivary levels of interferon (IFN)-gamma, interleukin (IL)-17, IL-21, and IL-22 with chronic periodontitis
Introduction
Periodontal diseases are progressive and destructive inflammatory conditions of the tooth-supporting tissues of multifactorial nature with pathogenesis related to several risk factors, including bacteria, host responses, and genetics. Although it has been recognized that chronic periodontitis (CP) is initiated and maintained in the first line by a complex polymicrobial infection,1 it is now thoroughly accepted that the innate susceptibility of the patient is the critical factor that will determine the destructive character of the disease. In this way, bacterial virulence factors either result directly in degradation of host tissues or induce the release of inflammatory mediators and chemokines that lead to tissue destruction.2
Among these biologic mediators, interferon (IFN)-γ, a pleiotropic cytokine, has demonstrated to possess potent proinflammatory actions in innate and adaptive immune responses not only by inducing the production of cytokines and chemokines,3, 4 but also by upregulating the expression of various membrane proteins including class I and II major histocompatibility complex (MHC) antigens, Fc receptors, leukocyte adhesion molecules, and B7 family antigens. Furthermore, IFN-γ is a potent activator of macrophage effector functions. It directs the synthesis, class switching, and secretion of immunoglobulins by B cells.5, 6
The activation of innate immunity almost synchronously leads to the activation of cell-mediated immunity.7 In this context, cytokines produced after the initial activation lead to the differentiation of naive CD4+ T cells towards one of the three functional subpopulations known today as T-helper (Th)1, Th2, and Th17 cells, based on the cytokine profiles they secrete. Since the initial description of Th1 and Th2 subpopulations,8 it has been attempted to explain the immunopathogenesis of periodontal diseases in one or other response profile, which has generated enormous controversy among researchers.2 Only until 2005, it was recognized the subset Th17 as a lineage of distinct CD4+ T cells,9 responsible for the production of the cytokines interleukin (IL)-17A, IL-17F, IL-21 and IL-22,10 which not only have a pro-inflammatory character at mucosal surfaces in response to extracellular pathogens11, 12 but also have been associated with autoimmunity.13 At this point, it is possible to argue that Th1, Th2, and Th17 subsets are potentially destructive from the tissue damage viewpoint.4 Nevertheless, it has been stated that IFN-γ influences Th cell phenotype development by inhibiting the differentiation of Th2/Th17 cell lineage and of the stimulation of Th1 development.5, 6, 9
Although several studies performed in gingival crevicular fluid (GCF) and gingival tissue samples have shown that the expression of both IFN-γ and/or Th17 cytokines might play a role in the etiopathogenesis of CP,14, 15, 16, 17, 18, 19, 20, 21 there is only limited information concerning the levels of these immunoregulatory factors in saliva samples and its relationship with the clinical manifestations of disease.22, 23, 24 As saliva has gained significant recognition as a biological sample for the detection of biochemical and cellular factors that may reflect the biological changes related to tissue damage observed in CP,24, 25, 26, 27, 28 this study aimed to investigate if the salivary levels of IL-17, IL-21, IL-22, and its ratio regarding IFN-γ salivary levels may be linked with the periodontal clinical status in a Colombian population.
Section snippets
Study population and inclusion/exclusion criteria
This descriptive, cross-sectional study was conducted at the Faculty of Dentistry, University of Antioquia in Medellín (Colombia) from January 2011 to December 2013. The study conformed to the ethical guidelines of the Helsinki Declaration and was evaluated and approved by the Institutional Ethics Committee for Human Studies. The sample size was calculated using a Sample Size Calculator (Raosoft® Inc., Seattle, WA, USA) on the basis of a previous study regarding the association of salivary
Reproducibility of measurements and sample size considerations
Intra-observer reproducibility was excellent for PD (ICC = 0.995 and 0.944 respectively, P < 0.008), and CAL (ICC = 0.998 and 0.984 respectively, P < 0.001) scores in each series of measures recorded per patient by the same examiner. Likewise, inter-observer reproducibility was excellent for both PD (ICC = 0.991–0.975, P < 0.002) and CAL scores (both ICC = 0.993, P < 0.001). Also, intra-observer reproducibility was excellent for IFN-γ (ICC = 0.904, P = 0.022), IL-17 (ICC = 0.991, P < 0.001), IL-21 (ICC = 0.993, P <
Discussion
Cytokines play a critical role in determining the strength, nature, and duration of immune responses in the pathogenesis of many inflammatory diseases including chronic periodontitis,2, 4, 13, 33, 34 hence cytokine profiles are of considerable value when studying disease mechanisms.14 Characteristic markers of Th1, Th2, and Th17 profiles have been described in diseased periodontal tissues, and several studies have demonstrated that both commensal and pathogenic oral bacteria are able to trigger
Authors’ contribution
Tobón-Arroyave SI handled the study concepts and design, supervised the acquisition of the data, accomplished the analysis and interpretation of data, and critically evaluated and supplemented the manuscript. Isaza-Guzmán DM and Martínez-Pabón MC participated in its design, carried out the ELISA procedures, acquisition and analysis of data, and manuscript preparation. Cardona-Vélez N, Gaviria-Correa DE, and Castaño-Granada MC participated in the design of the study, accomplished the recording
Funding
This study has been fully supported by a grant of the Research Development Committee of the University of Antioquia (CODI-Code 8700-1039).
Competing interests
None declared.
Ethical approval
Not required.
Acknowledgment
This study has been fully supported by a grant of the Research Development Committee of the University of Antioquia (CODI-Code 8700-1039).
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Cited by (39)
Levels of the interleukins 17A, 22, and 23 and the S100 protein family in the gingival crevicular fluid of psoriatic patients with or without periodontitis
2021, Anais Brasileiros de DermatologiaA review of T helper 17 cell-related cytokines in serum and saliva in periodontitis
2021, CytokineCitation Excerpt :Clinical studies in humans report higher IL-22 in GCF and gingival tissues of periodontitis affected subjects [110]. However, other have observed that IL-22 is not significantly different between periodontitis and health [77] or is poorly detectable by the assay [95,111]. Animal models of ligature-induced periodontitis report significantly higher gingival IL-22 mRNA expression at day 5 and 7 corresponding to moderate and peak disease periods [112], however, others report no significant differences [87].
T helper 17 cell-related cytokines in serum and saliva during management of periodontitis
2020, CytokineCitation Excerpt :However, during chronic inflammation, IL-17A also causes tissue degradation through upregulating RANKL expression by osteoblasts [66,67], inducing MMP-1, MMP-3, MMP-9 and MMP-13 and regulating tissue inhibitor of metalloproteinases-1 expression [68–71]. The decrease in salivary IL-17A is corroborated by a previous study [72], but other studies have observed no differences with treatment [37,73], no differences between health and disease [26,74,75], and lower [76,77] or higher concentrations in periodontitis compared to health [27,48,78,79]. IL-23 is a heterodimeric cytokine composed of the IL-23p19 and IL-12p40 subunits.
Periodontitis is associated with disease severity and anti-double stranded DNA antibody and interferon-gamma levels in patients with systemic lupus erythematosus
2019, Journal of Taibah University Medical SciencesCitation Excerpt :IFN-γ can increase T cell production and induce B cells to produce autoantibodies through the neutrophil extracellular traps pathway. The increase in IFN-γ causes activation of neutrophils, forming antibodies to DNA consisting of an immune complex, resulting in severe tissue inflammation.19 In vitro and in vivo studies in mouse models of SLE have demonstrated a high rate of periodontal disease and that IFN-γ contributed to the onset and progression of periodontitis.
Inflammatory cytokine profiles in the crevicular fluid around clinically healthy dental implants compared to the healthy contralateral side during the early stages of implant function
2019, Archives of Oral BiologyCitation Excerpt :For implants that just exercise the occlusion function, the changes in cytokines associated with bone tissue remodeling and immune adaptation in the crevicular fluid should appear more pronounced. IL-12p70, IL-18, IL-21, IL-23, VEGF-A, HGF, FGF-2 and IFN-γ are all associated with inflammatory infection and injury repair (Anil et al., 2014; Fokkema et al., 2003; Isaza-Guzman et al., 2015; Liukkonen, Gürsoy, Pussinen, Suominen, & Könönen, 2016; Pradeep, Hadge, Chowdhry, Patel, & Happy, 2009; Pradeep, Prapulla, Sharma, & Sujatha, 2011; Seghezzi et al., 1998). BDNF and TNF-α not only show significant differences between implants and natural teeth, but also show significant changes in time.