Purpose.Inflammation and tissue breakdown are led by an array of inflammatory destructive mediators associated with initiation and progression of inflammatory diseases like periodontitis. Current evidence shows that these inflammatory mediators have a definitive role in the pathogenesis of various systemic diseases with an inflammatory component. Interleukin-21 (IL-21) has been associated with systemic diseases like rheumatoid arthritis and Crohn’s disease that follow a chronic inflammatory cascade. Similarly recent studies have associated Interleukin-21 levels with periodontitis. This systematic review was aimed to assess the levels of IL-21 in subjects with periodontitis.Methods.A complete literature search was done in PubMed, Medline, Science Direct, and Cochrane databases and Google Scholar based on the inclusion/exclusion criteria. Six relevant articles were procured. Full text was read individually by two reviewers and data extraction was done based on STROBE statement.Results.After data extraction five observational and one interventional study were obtained. All the studies showed an increased expression of IL-21 in periodontitis and the interventional study showed reduction in IL-21 levels after nonsurgical periodontal therapy (NSP).Conclusion.Interleukin-21 levels are higher in periodontitis than controls. With this limited evidence further longitudinal studies are required to consider this as a definitive inflammatory marker.

Interleukin-21 (IL-21) has both anti- and pro-inflammatory roles associated with chronic inflammation. It causes tissue destruction by increasing pro-inflammatory cytokines and curbs the activity of certain immune cells that evoke an anti-inflammatory role. The aim of this study was to compare IL-21 levels in gingival crevicular fluid among patients with generalized chronic periodontitis (GCP), aggressive periodontitis, and healthy gingiva (HG) and to correlate IL-21 levels with clinical parameters. In this cross-sectional case-control study, 60 subjects were categorized into three groups: HG (n=20), generalized aggressive periodontitis (GAP; n=20), and GCP (n=20). IL-21 was measured using ELISA and results were correlated with clinical parameters including plaque index, gingival index, periodontal probing depth (PPD), and clinical attachment level (CAL). Mean IL-21 levels were 20.0±0.7 in HG, 25.9±0.9 in GCP, and 25.3±1.1 in GAP groups. Significant differences in IL-21 levels were found between HG versus GAP (P<0.05) and HG versus GCP (P<0.05). No statistically significant difference in IL-21 level was found between GCP versus GAP. IL-21 levels positively correlated with PPD (r=0.97) and CAL (r=0.93) in the GAP group and with PPD (r=0.92) and CAL (r=0.96) in the GCP group. Although periodontitis pathophysiology involves complex interplay between pro- and anti-inflammatory signaling, data on IL-21 revealed elevated levels in both GCP and GAP. Further longitudinal studies are required to characterize and determine the diagnostic value of IL-21 as a reliable biomarker in periodontal disease. Although further longitudinal studies are necessary, IL-21 may serve as a potential inflammatory biomarker in screening for generalized chronic and aggressive periodontitis.