Association study between salivary levels of interferon (IFN)-gamma, interleukin (IL)-17, IL-21, and IL-22 with chronic periodontitis

https://doi.org/10.1016/j.archoralbio.2014.09.002Get rights and content

Highlights

  • IFN-γ and/or Th17 cytokines might play a role in the etiopathogenesis of CP.

  • Saliva samples may reflect the biological changes related to tissular damage observed in CP.

  • Disease status showed a strong association with salivary levels of IFN-γ and IFN-γ/IL-22 ratio.

  • Th17 cytokines were not of predictive value for health/disease status.

  • Age stratum showed a synergistic interaction effect on IFN-γ levels.

Abstract

Objective

To investigate if the salivary levels of IL-17, IL-21, IL-22, and its ratio regarding salivary IFN-γ may be linked with the periodontal clinical status.

Design

One hundred and five chronic periodontitis (CP) subjects and 44 healthy controls (HC) were recruited. Periodontal status was assessed based on full-mouth clinical periodontal measurements. Cytokine salivary levels were analyzed by ELISA. The association between the analytes with CP was analyzed using a binary logistic regression model.

Results

A statistically significant increase in salivary levels of IFN-γ and IFN-γ/IL-22 ratio in CP group could be detected, but there was no significant domination of any Th17 cytokine that could be of predictive value for health/disease status. Univariate and binary logistic regression analyses revealed a strong and independent association of IFN-γ salivary levels and IFN-γ/IL-22 ratio with disease status. An interaction effect of ageing on IFN-γ levels also could be noted.

Conclusion

While salivary levels of IFN-γ and IFN-γ/IL-22 ratio may act as strong/independent indicators of the amount and extent of periodontal breakdown, the low detection frequency of Th17 cytokines in saliva samples make these determinations useless for the detection of disease presence and/or its severity.

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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