Salivary Levels of IL-21 as a Potential Marker of Stage III Grade C Periodontitis

Year 2021, Volume: 11 Issue: 4, 878 - 883, 26.10.2021

Ayse Ege Selman , Nimet Gül Görgülü , Başak Doğan

https://doi.org/10.33808/clinexphealthsci.989487

Cited By: 1

Abstract

Objective: The onset, severity and progression of periodontal diseases are mainly related to the inflammatory host response against periodontal pathogens. The aim of this study was to evaluate salivary interleukin (IL) -1β, IL-13, IL-21 and IL-33 levels in patients with stage III grade C periodontitis and compare it with periodontally healthy individuals.
Methods: A total of 58 individuals, including 28 periodontally healthy and 30 stage III grade C periodontitis patients were included in this study. Periodontal parameters including plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) were measured. Saliva samples were obtained from all patients. Salivary interleukin (IL) -1β, IL-13, IL21, IL-33 levels were assessed using enzyme-linked immunosorbent assay (ELISA).
Results: All clinical parameters were significantly higher in periodontitis patients compared to healthy individuals (p<0.001). Elevated salivary IL-1β and IL-21 levels were found in the periodontitis group compared to healthy ones (p=0.009 and p<0.001, respectively). However, IL-13 and IL-33 levels were similar in both groups (p= 0.92). IL-1β was significantly correlated with both clinical and biochemical parameters but IL-21 was correlated with only clinical parameters.
Conclusion: This study showed that elevated salivary IL-21 and IL-1β levels are associated with periodontitis and might be used as a marker for the diagnosis of periodontitis.

Keywords

Periodontitis, interleukin-1 beta, interleukin-13, interleukin-21, interleukin-33

References

• Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.
• Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014;64:57-80.
• Dinarello CA. Historical insights into cytokines. Eur J Immunol 2007;37 Suppl 1:S34-45.
• Teles R, Moss K, Preisser JS, Genco R, Giannobile WV, Corby P, Garcia N, Jared H, Torresyap G, Salazar E, Moya J, Howard C, Schifferle R, Falkner KL, Gillespie J, Dixon D, Cugini M. Patterns of periodontal disease progression based on linear mixed models of clinical attachment loss. J Clin Periodontol 2018;45:15-25.
• Barksby HE, Lea SR, Preshaw PM, Taylor JJ. The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol 2007;149:217-225.
• Kc S, Wang XZ, Gallagher JE. Diagnostic sensitivity and specificity of host-derived salivary biomarkers in periodontal disease amongst adults: Systematic review. J Clin Periodontol 2020;47:289-308.
• Gumus P, Nizam N, Nalbantsoy A, Ozcaka O, Buduneli N. Saliva and serum levels of pentraxin-3 and interleukin-1beta in generalized aggressive or chronic periodontitis. J Periodontol 2014;85:e40-46
• Medara N, Lenzo JC, Walsh KA, Reynolds EC, Darby IB, O'Brien-Simpson NM. A review of T helper 17 cell-related cytokines in serum and saliva in periodontitis. Cytokine 2021;138:155340.
• Yamazaki K, Nakajima T. Antigen specificity and T-cell clonality in periodontal disease. Periodontol 2000 2004;35:75-100.
• Pradeep AR, Roopa Y, Swati PP. Interleukin-4, a T-helper 2 cell cytokine, is associated with the remission of periodontal disease. J Periodontal Res 2008;43:712-716.
• Jakubzick C, Kunkel SL, Puri RK, Hogaboam CM. Therapeutic targeting of IL-4- and IL-13-responsive cells in pulmonary fibrosis. Immunol Res 2004;30:339-349.
• Palmqvist P, Lundberg P, Persson E, Johansson A, Lundgren I, Lie A, Conaway HH, Lerner UH. Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway. J Biol Chem 2006;281:2414-2429.
• Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 1993;362:248-250.
• Miranda TS, Heluy SL, Cruz DF, da Silva HDP, Feres M, Figueiredo LC, Duarte PM. The ratios of pro-inflammatory to anti-inflammatory cytokines in the serum of chronic periodontitis patients with and without type 2 diabetes and/or smoking habit. Clin Oral Investig 2019;23:641-650.
• Zein Elabdeen HR, Mustafa M, Ali R, Bolstad AI. Cytokine profile in gingival crevicular fluid and plasma of patients with aggressive periodontitis. Acta Odontol Scand 2017;75:616-622.
• Gorgun EP, Toker H, Tas A, Alpan AL, Sari I, Silig Y. IL-13 gene polymorphisms (-1112 C/T and -1512 A/C) in patients with chronic and aggressive periodontitis: Effects on GCF and outcome of periodontal therapy. Niger J Clin Pract 2021;24:965-972.
• Al-Hamoudi N, Alsahhaf A, Al Deeb M, Alrabiah M, Vohra F, Abduljabbar T. Effect of scaling and root planing on the expression of anti-inflammatory cytokines (IL-4, IL-9, IL-10, and IL-13) in the gingival crevicular fluid of electronic cigarette users and non-smokers with moderate chronic periodontitis. J Periodontal Implant Sci 2020;50:74-82.
• Emingil G, Gurkan A, Atilla G, Kantarci A. Subantimicrobial-dose doxycycline and cytokine-chemokine levels in gingival crevicular fluid. J Periodontol 2011;82:452-461.
• Brandt K, Singh PB, Bulfone-Paus S, Ruckert R. Interleukin-21: a new modulator of immunity, infection, and cancer. Cytokine Growth Factor Rev 2007;18:223-232.
• Gharibi T, Majidi J, Kazemi T, Dehghanzadeh R, Motallebnezhad M, Babaloo Z. Biological effects of IL-21 on different immune cells and its role in autoimmune diseases. Immunobiology 2016;221:357-367.
• Lubberts E. Th17 cytokines and arthritis. Semin Immunopathol 2010;32:43-53.
• Beklen A, Ainola M, Hukkanen M, Gurgan C, Sorsa T, Konttinen YT. MMPs, IL-1, and TNF are regulated by IL-17 in periodontitis. J Dent Res 2007;86:347-351.
• Allam JP, Duan Y, Heinemann F, Winter J, Gotz W, Deschner J, Wenghoefer M, Bieber T, Jepsen S, Novak N. IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions. J Clin Periodontol 2011;38:879-886.
• Adibrad M, Deyhimi P, Ganjalikhani Hakemi M, Behfarnia P, Shahabuei M, Rafiee L. Signs of the presence of Th17 cells in chronic periodontal disease. J Periodontal Res 2012;47:525-531.
• Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol 2016;9:1163-1172.
• Lin PY, Jen HY, Chiang BL, Sheu F, Chuang YH. Interleukin-21 suppresses the differentiation and functions of T helper 2 cells. Immunology 2015;144:668-676.
• Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, Nares S, Osorio M, Wahl SM. Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis. J Autoimmun 2012;39:294-303.
• Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 2012;181:8-18.
• Tahmasebinia F, Pourgholaminejad A. The role of Th17 cells in auto-inflammatory neurological disorders. Prog Neuropsychopharmacol Biol Psychiatry 2017;79:408-416.
• Lokhande RV, Ambekar JG, Bhat KG, Dongre NN. Interleukin-21 and its association with chronic periodontitis. J Indian Soc Periodontol 2019;23:21-24.
• Gumus P, Nizam N, Nalbantsoy A, Ozcaka O, Buduneli N. Saliva, Serum Levels of Interleukin-21, -33 and Prostaglandin E2 in Patients with Generalised Aggressive or Chronic Periodontitis. Oral Health Prev Dent 2017;15:385-390.
• Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005;23:479-490.
• da Luz FA, Oliveira AP, Borges D, Brigido PC, Silva MJ. The physiopathological role of IL-33: new highlights in bone biology and a proposed role in periodontal disease. Mediators Inflamm 2014;2014:342410.
• Saglam M, Koseoglu S, Aral CA, Savran L, Pekbagriyanik T, Cetinkaya A. Increased levels of interleukin-33 in gingival crevicular fluids of patients with chronic periodontitis. Odontology 2017;105:184-190.
• Buduneli N, Ozcaka O, Nalbantsoy A. Interleukin-33 levels in gingival crevicular fluid, saliva, or plasma do not differentiate chronic periodontitis. J Periodontol 2012;83:362-368.
• Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol 2018;45 Suppl 20:S162-S170.
• Silness J, Loe H. Periodontal Disease in Pregnancy. Ii. Correlation between Oral Hygiene and Periodontal Condtion. Acta Odontol Scand 1964;22:121-135.
• Loe H, Silness J. Periodontal Disease in Pregnancy. I. Prevalence and Severity. Acta Odontol Scand 1963;21:533-551.
• Afacan B, Ozturk VO, Emingil G, Kose T, Bostanci N. Alarm anti-protease trappin-2 negatively correlates with proinflammatory cytokines in patients with periodontitis. J Periodontol 2018;89:58-66.
• Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol 2011;38 Suppl 11:85-105.
• Wang Z, Chen F, Zhai R, Zhang L, Su L, Lin X, Thompson T, Christiani DC. Plasma neutrophil elastase and elafin imbalance is associated with acute respiratory distress syndrome (ARDS) development. PLoS One 2009;4:e4380.
• Into T, Inomata M, Kanno Y, Matsuyama T, Machigashira M, Izumi Y, Imamura T, Nakashima M, Noguchi T, Matsushita K. Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue. Clin Exp Immunol 2006;145:545-554.
• Yin L, Swanson B, An J, Hacker BM, Silverman GA, Dale BA, Chung WO. Differential effects of periopathogens on host protease inhibitors SLPI, elafin, SCCA1, and SCCA2. J Oral Microbiol 2010;2.
• Caucheteux SM, Hu-Li J, Guo L, Bhattacharyya N, Crank M, Collins MT, Paul WE. IL-1beta enhances inflammatory TH2 differentiation. J Allergy Clin Immunol 2016;138:898-901 e894.
• Yi JS, Cox MA, Zajac AJ. Interleukin-21: a multifunctional regulator of immunity to infections. Microbes Infect 2010;12:1111-1119.
• Mootha A, Malaiappan S, Jayakumar ND, Varghese SS, Toby Thomas J. The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review. Int J Inflam 2016;2016:3507503.
• Dutzan N, Vernal R, Vaque JP, Garcia-Sesnich J, Hernandez M, Abusleme L, Dezerega A, Gutkind JS, Gamonal J. Interleukin-21 expression and its association with proinflammatory cytokines in untreated chronic periodontitis patients. J Periodontol 2012;83:948-954.
• Koseoglu S, Hatipoglu M, Saglam M, Enhos S, Esen HH. Interleukin-33 could play an important role in the pathogenesis of periodontitis. J Periodontal Res 2015;50:525-534.