INTRODUCTION:

Periodontal diseases are a group of inflammatory disorders that are caused by pathogenic bacteria in the sub gingival biofilm leading to association with impaired host immune response and connective tissue breakdown. The bacterial challenge results in the release of various cytokines by the gingival epithelium, leading to an uncontrolled inflammation that leads to tooth loss in adults from different populations. [1-3]

Periodontitis progresses without causing severe discomfort in the oral cavity as it’s a chronic disease and patients often report for treatment only after the considerable destruction has taken place.[4]Thus, there is a need to diagnose periodontitis in its early stages using an easy, safe, and easily accessible method. Currently periodontitis is diagnosed using radiography and using clinical measurements such as probing pocket depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL).

Although these traditional clinical measurements are time-consuming and yield limited information, they are indicators of only previous periodontal disease rather than current disease activity. Moreover, they are inadequate for predicting susceptible individuals who might be at risk of periodontitis in the future. Hence a convenient diagnostic tool

CYTOKINES:

Cytokines are soluble proteins and they act messengers to transmit signals from one cell to another. They play a key role in mediating inflammation. Cytokines are able to induce their own expressions in either an autocrine or paracrine fashion, and they have pleiotropic effects on a large number of cells. [5,6] Cytokines bind to cell surface receptors and trigger a sequence of intra cellular events that lead ultimately to the production of proteins by the target cell, which alters the cells behaviour.

Cytokines play a key role at all stages of the immune response in periodontal disease. The biochemical pathways leading to cytokine secretion during the development of periodontitis involve signalling via the interaction of microbe associated molecular patterns (MAMPS, e.g., LPS, DNA, fimbriae, etc.) and pattern recognition receptors (PRR, e.g., Toll-like receptors (TLR) and NOD-like receptors (NLR) which are active on a wide range of cells. [7] Some of these important pro-inflammatory cytokines are IL-1alpha, IL-1beta, IL-6 and TNF alpha etc.

SALIVA AS A DIAGNOSTIC TOOL IN PERIODONTITIS:

Saliva is an optimal biological fluid which can serve as the diagnostic tool for periodontitis. Human saliva contains numerous molecular components that contribute to host defenses against bacterial colonization and periodontal disease. The collection of saliva is safe, non-invasive, and simple, and saliva can be collected repeatedly with minimum discomfort to the patient. [8, 9]

In terms of periodontal diagnosis, whole saliva not only is advantageous for its ease of collection but also has elements which reflect the activity of all periodontal sites and therefore provides an indication of disease status in the mouth as a whole rather than at individual sites as with GCF analysis. [10]

Studies of the immunopathogenesis of periodontitis and analysis of mediators in saliva have allowed the identification of many potentially useful biomarkers. Convenient measurement of these biomarkers using chairside analytical devices could form the basis for diagnostic tests which will aid the clinician and the patient in periodontitis management. [11, 12]

INTERLEUKIN1:

Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and haematopoiesis. Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors. [13]

IL-1𝛽 is produced by a wide range of periodontal tissues and immune cells and, as such, is considered to have multiple roles in innate and adaptive immune responses to plaque bacteria which feature in the pathogenesis of periodontitis. [14] IL-1𝛽 acts (often in synergy with TNF-𝛼 and prostaglandin E2 (PGE2) plays a role in inflammation and also regulates neutrophil emigration from the circulation into the periodontium. In adaptive immunity, IL-1𝛽 stimulates antigen presentation by APCs and influences T-cell development and phenotype.

A consensus paper of The 7th European Workshop on Periodontal Disease recently reported that IL-1𝛽, TNF-𝛼, IL- 6, and receptor activator of nuclear factor kappa-B ligand (RANKL) are cytokines for which there is the substantial evidence for having a central role in cytokine networks in periodontal diseases. [15] This current review focuses on the role of salivary interleukin 1 level in chronic periodontitis.

STUDIES COMPARING SALIVARY LEVELS OF INTERLEUKIN 1 IN CHRONIC PERIODONTITIS AND HEALTH:

Interleukin-1β is a resulting product of inflammatory and infectious stimuli, contributing to the development of an inflammatory condition. The IL-1β active form shows immune potentiating effects, mediating inflammatory responses, bone resorption, leading to apoptosis, cell proliferation and differentiation in response to inflammatory stimuli such as bacterial LPS, promoting recruitment of phagocytes, angiogenesis, epithelial cell repair, and regulation of cytokines and chemokine production by other immune cells at the site of infection or injury, being it an orchestrating cytokine during the immune response. [13-14]

Despite the recognized diagnostic potential of saliva, only a few reports have attempted to correlate the levels of cytokines in saliva with the periodontal condition of the subjects.

Miller et al. suggested that levels of salivary IL-1β were significantly higher in patients with periodontal disease than in controls, and they were correlated with individual clinical parameters indicative of periodontal disease. Further, combined elevated salivary levels of IL-1β and matrix metalloproteinase-8 increased the risk of experiencing periodontal disease 45-fold. [15]

Ng et al. concluded that salivary IL-1β levels were found in greater abundance in samples of 110 diseased untreated dental patients as opposed to interleukin-6 and PGE2. [16] These results showed a greater degree of correlation between IL-1β salivary levels and periodontal disease status than any of the other screened mediators.

Scannapieco et al in 2007 conducted a study comparing a 40-subject cohort with significant alveolar bone loss over a 5-year period with 40-age-matched control subjects having no alveolar bone loss. Salivary biomarkers were assayed at baseline and they found a positive association between alveolar bone loss and IL-1β salivary concentrations. [17]

Sexton et al in 2011 have done a study on 68-participant group with chronic periodontitis and had IL-1 β, IL-8, MIP- 1α, MMP-8, OPG, and TNF-α salivary cytokine levels screened. The study concluded that salivary levels of IL-1β reflected disease severity and response to therapy suggesting its potential utility for monitoring periodontal disease status. [18]

S.I. Tobon-Arroyave in 2008, have done a study to assess the concentration of the pro-inflammatory cytokine 1β in saliva of periodontally disease and healthy patients and their relationship with the periodontal status. Whole saliva is used as a sampling method in terms of immunological purpose in periodontal disease and suggested that the elevated IL-1 concentration may be one of the host response components associated to the clinical manifestations of periodontal disease. [19]

Thus there is a strong evidence to suggest that salivary IL-1𝛽 is a good biomarker of periodontitis in as much as measurement of IL-1𝛽 can discriminate periodontitis samples from those provided by healthy volunteers; however this finding has not been replicated in all studies. [20-22]

CONCLUSION:

IL- 1β levels would be associated with periodontal disease onset, severity, and progress as this cytokine showed to have a strong correlation with many clinical parameters evaluated and might be reliable to predict how an individual responds to periodontal diseases after a treatment. Saliva is an optimal biological fluid to serve as the diagnostic tool for periodontitis. The collection of saliva is safe, non-invasive, and simple, and saliva can be collected repeatedly with minimum discomfort to the patient.

Hence salivary IL- 1β can be used as a diagnostic biomarker for assessing the progression of periodontal disease. However there needs to be an approach to the unbiased selection of markers using “salavomics” coupled with more substantial, longitudinal, clinical studies in order to develop this field further. There is also a need to develop a practical approach to chair side analysis which will enable the dental clinician to efficiently and accurately assess periodontitis disease activity.

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Received on 23.07.2017 Modified on 18.08.2017

Research J. Pharm. and Tech. 2018; 11(1): 390-392.

DOI: 10.5958/0974-360X.2018.00071.9