Cytokine Levels in Gingival Tissues As an Indicator to Understand Periodontal Disease Severity

Overview

Journal Curr Res Immunol

Specialty Allergy & Immunology

Date 2024 Jul 19

PMID 39026560

Authors

Pratebha Balu

Agiesh Kumar Balakrishna Pillai

Vignesh Mariappan

Sudhakar Ramalingam

Affiliations

Soon will be listed here.

Abstract

Cytokines regulate periodontal pathogenesis and are relevant estimates of current disease activity. There is sparse information on status of cytokine protein levels in periodontal pocket (gingival) tissues. The current study analysed proteins and transcripts of selected cytokines in varying severity of periodontal disease and elucidated cytokine/cytokine ratios that best indicated periodontal disease severity, in gingival tissues. A total of 92 participants comprising of generalised moderate periodontitis (GMP, n = 18), generalised severe periodontitis (GSP, n = 46) and periodontally healthy controls (PHC, n = 25) were recruited for the study. Interproximal gingival tissue samples were utilised for cytokine protein estimation and mRNA quantification by qRT-PCR and ELISA respectively. Selected key pro and anti-inflammatory cytokines, also representative of various Th subsets were analysed. ROC curve analysis was performed and Youden index was calculated for individual cytokines and pro/anti-inflammatory cytokine ratio to estimate the best indicator of periodontal severity/progression in tissues. IL-1β, TGF-β and IFN-γ cytokine protein levels varied significantly (p ≤ 0.05) with severity of periodontal disease between groups. On comparison between deep and shallow sites within same participant, deep sites showed significant elevation of TGF-β (p ≤ 0.01) and IFN-γ (p ≤ 0.05) and IL-17 cytokines and shallow sites showed elevation of IL-4(p ≤ 0.01) and IL-1β (p ≤ 0.05) cytokines. Analysis of transcripts showed IFN-γ and IL-1β transcript predominance in GSP (p = 0.01) compared to PHC. ROC analysis illustrated 97% sensitivity, 93% specificity with Youden index of 90% for IL-1β cytokine and 81%sensitivity, 79% specificity with a Youden index of 60% for IL-1β/TGF-β ratio In periodontal pocket tissue, a lack of distinct predominance of specific cytokines between study groups or between shallow and deep sites affected by periodontal disease was observed. However, ROC analysis of cytokines revealed IL-1β cytokine and IL-1β/TGF-β ratio as promising indicators of periodontal disease severity in gingival tissues.

References

Becerik S, Ozturk V, Atmaca H, Atilla G, Emingil G . Gingival crevicular fluid and plasma acute-phase cytokine levels in different periodontal diseases. J Periodontol. 2012; 83(10):1304-13. DOI: 10.1902/jop.2012.110616. View

Berglundh T, Liljenberg B, Lindhe J . Some cytokine profiles of T-helper cells in lesions of advanced periodontitis. J Clin Periodontol. 2002; 29(8):705-9. DOI: 10.1034/j.1600-051x.2002.290807.x. View

Van Dyke T, Bartold P, Reynolds E . The Nexus Between Periodontal Inflammation and Dysbiosis. Front Immunol. 2020; 11:511. PMC: 7136396. DOI: 10.3389/fimmu.2020.00511. View

Pradeep A, Roopa Y, Swati P . Interleukin-4, a T-helper 2 cell cytokine, is associated with the remission of periodontal disease. J Periodontal Res. 2008; 43(6):712-6. DOI: 10.1111/j.1600-0765.2007.01079.x. View

Gaffen S, Hajishengallis G . A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res. 2008; 87(9):817-28. PMC: 2692983. DOI: 10.1177/154405910808700908. View

Dutzan N, Gamonal J, Silva A, Sanz M, Vernal R . Over-expression of forkhead box P3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL) -17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis. J Clin Periodontol. 2009; 36(5):396-403. DOI: 10.1111/j.1600-051X.2009.01390.x. View

Kotake S, Yago T, Kawamoto M, Nanke Y . Role of osteoclasts and interleukin-17 in the pathogenesis of rheumatoid arthritis: crucial 'human osteoclastology'. J Bone Miner Metab. 2011; 30(2):125-35. DOI: 10.1007/s00774-011-0321-5. View

Teles R, Sakellari D, Teles F, Konstantinidis A, Kent R, Socransky S . Relationships among gingival crevicular fluid biomarkers, clinical parameters of periodontal disease, and the subgingival microbiota. J Periodontol. 2010; 81(1):89-98. PMC: 2805280. DOI: 10.1902/jop.2009.090397. View

Pan W, Wang Q, Chen Q . The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 2019; 11(3):30. PMC: 6828663. DOI: 10.1038/s41368-019-0064-z. View

10.

Honda T, Domon H, Okui T, Kajita K, Amanuma R, Yamazaki K . Balance of inflammatory response in stable gingivitis and progressive periodontitis lesions. Clin Exp Immunol. 2006; 144(1):35-40. PMC: 1809628. DOI: 10.1111/j.1365-2249.2006.03028.x. View

11.

Johnson R, Wood N, Serio F . Interleukin-11 and IL-17 and the pathogenesis of periodontal disease. J Periodontol. 2004; 75(1):37-43. DOI: 10.1902/jop.2004.75.1.37. View

12.

McGEE J, Tucci M, Edmundson T, Serio C, Johnson R . The relationship between concentrations of proinflammatory cytokines within gingiva and the adjacent sulcular depth. J Periodontol. 1998; 69(8):865-71. DOI: 10.1902/jop.1998.69.8.865. View

13.

Storey J, Madeoy J, Strout J, Wurfel M, Ronald J, Akey J . Gene-expression variation within and among human populations. Am J Hum Genet. 2007; 80(3):502-9. PMC: 1821107. DOI: 10.1086/512017. View

14.

Duarte P, de Lorenzo Abreu L, Vilela A, Feres M, Giro G, Miranda T . Protein and mRNA detection of classic cytokines in corresponding samples of serum, gingival tissue and gingival crevicular fluid from subjects with periodontitis. J Periodontal Res. 2018; 54(2):174-179. DOI: 10.1111/jre.12617. View

15.

Silver N, Cotroneo E, Proctor G, Osailan S, Paterson K, Carpenter G . Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states. BMC Mol Biol. 2008; 9:64. PMC: 2492873. DOI: 10.1186/1471-2199-9-64. View

16.

Gorska R, Gregorek H, Kowalski J, Laskus-Perendyk A, Syczewska M, Madalinski K . Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol. 2004; 30(12):1046-52. DOI: 10.1046/j.0303-6979.2003.00425.x. View

17.

Toker H, Poyraz O, Eren K . Effect of periodontal treatment on IL-1beta, IL-1ra, and IL-10 levels in gingival crevicular fluid in patients with aggressive periodontitis. J Clin Periodontol. 2008; 35(6):507-13. DOI: 10.1111/j.1600-051X.2008.01213.x. View

18.

Dutzan N, Vernal R, Hernandez M, Dezerega A, Rivera O, Silva N . Levels of interferon-gamma and transcription factor T-bet in progressive periodontal lesions in patients with chronic periodontitis. J Periodontol. 2009; 80(2):290-6. DOI: 10.1902/jop.2009.080287. View

19.

Gemmell E, Seymour G . Immunoregulatory control of Th1/Th2 cytokine profiles in periodontal disease. Periodontol 2000. 2004; 35:21-41. DOI: 10.1111/j.0906-6713.2004.003557.x. View

20.

Wassall R, Preshaw P . Clinical and technical considerations in the analysis of gingival crevicular fluid. Periodontol 2000. 2015; 70(1):65-79. DOI: 10.1111/prd.12109. View