This study aimed to evaluate the levels of interleukin-18 and tumor necrosis factor-alpha in gingival crevicular fluid of diabetic children with gingivitis.
Eighty-eight children (44 with type 1 diabetes mellitus and 44 systemically healthy) were recruited for the study. The children were divided into four subgroups based on their periodontal and systemic condition: (1) systemically and periodontally healthy children (H), (2) systemically healthy children with gingivitis (G), (3) periodontally healthy children with T1DM (T1DM + H), and (4) children with T1DM and gingivitis (T1DM + G). The plaque index, gingival index, probing pocket depth, and GCF volume were recorded. The IL-18 and TNF-α levels in GCF were determined by ELISA.
The clinical periodontal parameters, GCF IL-18 level, and TNF-α level were similar between diabetic and systemically healthy children (p > 0.05). The gingivitis subgroups had a significantly higher GI, PI, PPD, GCF volume, and TNF-α total amounts than the H subgroups (p < 0.0001). The IL-18 concentrations in the gingivitis subgroups were significantly lower than in the periodontally healthy subgroups.
In diabetic children with good metabolic control, T1DM did not affect the GCF levels of IL-18 and TNF-α in the presence of gingivitis. However, increased GCF TNF-α levels in children with gingivitis confirm that TNF-α is closely related to gingival inflammation.
Type 1 diabetes mellitus is not associated with GCF interleukin-18 and tumor necrosis factor-alpha levels in children with gingivitis.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Altinova AE, Engin D, Akbay E, Akturk M, Toruner F, Ersoy R, Arslan M (2010) Association of polymorphisms in the IL-18 and IL-12 genes with susceptibility to type 1 diabetes in Turkish patients. J Endocrinol Investig 33:451–454. https://doi.org/10.1007/BF03346623
Sridharan S, Sravani P, Satyanarayan A, Kiran K, Shetty V (2017) Salivary alkaline phosphatase as a noninvasive marker for periodontal disease in children with uncontrolled type 1 diabetes mellitus. J Clin Pediatr Dent 41(1):70–74. https://doi.org/10.17796/1053-4628-41.1.70
Lamster IB, Lalla E, Borgnakke WS, Taylor GW (2008) The relationship between oral health and diabetes mellitus. J Am Dent Assoc 139:19–24. https://doi.org/10.14219/jada.archive.2008.0363
Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE (2005) Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 43:5721–5732. https://doi.org/10.1128/JCM.43.11.5721-5732.2005
Preshaw PM, Alba AL, Herrera D, Jepsen S, Konstantinidis A, Makrilakis K, Taylor R (2012) Periodontitis and diabetes: a two-way relationship. Diabetologia 55:21–31. https://doi.org/10.1007/s00125-011-2342-y
Graves DT, Liu R, Alikhani M, Al-Mashat H, Trackman PC (2006) Diabetes-enhanced inflammation and apoptosis—impact on periodontal pathology. J Dent Res 85:15–21. https://doi.org/10.1177/154405910608500103
Orozco A, Gemmell E, Bickel M, Seymour GJ (2006) Interleukin-1 β, interleukin-12 and interleukin-18 levels in gingival fluid and serum of patients with gingivitis and periodontitis. Oral Microbiol Immunol 21:256–260. https://doi.org/10.1177/154405910608500103
Ülker AE, Tulunoglu Ö, Özmeric N, Can M, Demirtas S (2008) The evaluation of cystatin C, IL-1β, and TNF-α levels in total saliva and gingival crevicular fluid from 11-to 16-year-old children. J Periodontol 79:854–860. https://doi.org/10.1902/jop.2008.070422
Graves CE, Berkowitz RJ, Proskin HM, Chase I, Weinstein P, Billings R (2004) Clinical outcomes for early childhood caries: influence of aggressive dental surgery. J Dent Child 71:114–117
Graves DT, Cochran D (2003) The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 74:391–401
Türer ÇC, Ballı U, Güven B (2017) Fetuin-A, serum amyloid A and tumor necrosis factor alpha levels in periodontal health and disease. Oral Dis 23:379–386. https://doi.org/10.1111/odi.12625
Ertugrul AS, Sahin H, Dikilitas A, Alpaslan N, Bozoglan A (2013) Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis. J Periodontal Res 48:44–51. https://doi.org/10.1111/j.1600-0765.2012.01500.x
Qiao YC, Chen YL, Pan YH, Tian F, Xu Y, Zhang XX, Zhao HL (2017) The change of serum tumor necrosis factor alpha in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. PLoS One 12:e0176157
Duque C, Joao MFD, Camargo GADCG, Teixeira GS, Machado TS, Azevedo RDS, Mattos-Graner RDO (2017) Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus. J Appl Oral Sci 25:217–226. https://doi.org/10.1590/1678-77572016-0196
Kaplanski G (2018) Interleukin-18: biological properties and role in disease pathogenesis. Immunol Rev 281:138–153. https://doi.org/10.1111/imr.12616
Campos BOD, Fischer RG, Gustafsson A, Figueredo CMDS (2012) Effectiveness of non-surgical treatment to reduce il-18 levels in the gingival crevicular fluid of patients with periodontal disease. Braz Dent J 23:428–432. https://doi.org/10.1590/S0103-64402012000400020
Kashiwamura SI, Ueda H, Okamura H (2002) Roles of interleukin-18 in tissue destruction and compensatory reactions. J Immunother 25:4–11
Harms RZ, Yarde DN, Guinn Z, Lorenzo-Artega KM, Corley KP, Cabrera MS, Sarvetnick NE (2015) Increased expression of IL-18 in the serum and islets of type 1 diabetics. Mol Immunol 64:306–312. https://doi.org/10.1016/j.molimm.2014.12.012
Figueredo CM, Rescala B, Teles RP, Teles FP, Fischer RG, Haffajee AD, Gustafsson A (2008) Increased interleukin-18 in gingival crevicular fluid from periodontitis patients. Oral Microbiol Immunol 23:173–176. https://doi.org/10.1111/j.1399-302X.2007.00408.x
Pradeep AR, Daisy H, Hadge P, Garg G, Thorat M (2009) Correlation of gingival crevicular fluid interleukin-18 and monocyte chemoattractant protein-1 levels in periodontal health and disease. J Periodontol 80:1454–1461. https://doi.org/10.1902/jop.2009.090117
Dakovic D, Pavlovic MD (2008) Periodontal disease in children and adolescents with type 1 diabetes in Serbia. J Periodontol 79:987–992
Al-Khabbaz AK, Al-Shammari KF, Hasan A, Abdul-Rasoul M (2013) Periodontal health of children with type 1 diabetes mellitus in Kuwait: a case-control study. Med Princ Pract 22:144–149. https://doi.org/10.1159/000342624
American Diabetes Association (2019) Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care 42:90–102. https://doi.org/10.2337/dc19-S013
Silness J, Löe H (1964) Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition. Acta Odontol. Scand 22:121–135. https://doi.org/10.3109/00016356408993968
Löe H, Silness J (1963) Periodontal disease in pregnancy I. Prevalence and severity. Acta Odontol Scand 2:533–551. https://doi.org/10.3109/00016356309011240
Franchini R, Petri A, Migliario M, Rimondini L (2011) Poor oral hygiene and gingivitis are associated with obesity and overweight status in paediatric subjects. J Clin Periodontol 38:1021–1028. https://doi.org/10.1111/j.1600-051X.2011.01770.x
Doğusal G, Afacan B, Bozkurt E, Sönmez I (2018) Gingival crevicular fluid and salivary resistin and tumor necrosis factor-alpha levels in obese children with gingivitis. J Periodontol 89:973–982. https://doi.org/10.1002/JPER.17-0613
Altinova AE, Yetkin I, Akbay E, Bukan N, Arslan M (2008) Serum IL-18 levels in patients with type 1 diabetes: relations to metabolic control and microvascular complications. Cytokine 42:217–221. https://doi.org/10.1016/j.cyto.2008.02.006
Brunner E, Puri ML (2001) Nonparametric methods in factorial designs. Stat Pap 42:1–52
Clerehugh V (2008) Periodontal diseases in children and adolescents. Br Dent J 204:469
Wolff LF (2014) Diabetes and periodontal disease. Am J Dent 27:127–128
Eley BM, Cox SW (2000) Proteolytic and hydrolytic enzymes from putative periodontal pathogens: characterization, molecular genetics, effects on host defenses and tissues and detection in gingival crevice fluid. Periodontol 2000 31:105–124. https://doi.org/10.1034/j.1600-0757.2003.03107.x
Thomadaki K, Helmerhorst EJ, Tian N, Sun X, Siqueira WL, Walt DR, Oppenheim FG (2011) Whole-saliva proteolysis and its impact on salivary diagnostics. J Dent Res 90:1325–1330. https://doi.org/10.1177/0022034511420721
Laugisch O, Schacht M, Guentsch A, Kantyka T, Sroka A, Stennicke HR, Pfister W, Sculean A, Potempa J, Eick S (2012) Periodontal pathogens affect the level of protease inhibitors in gingival crevicular fluid. Mol Oral Microbiol 27:45–56. https://doi.org/10.1111/j.2041-1014.2011.00631.x
Shapiro L, Goldman H, Bloom A (1979) Sulcular exudate flow in gingival inflammation. J Periodontol 50:301–304. https://doi.org/10.1902/jop.1922.214.171.1241
Griffiths GS, Sterne JAC, Wilton JMA, Eaton KA, Johnson NW (1992) Associations between volume and flow rate of gingival crevicular fluid and clinical assessments of gingival inflammation in a population of British male adolescents. J Clin Periodontol 19:464–470. https://doi.org/10.1111/j.1600-051X.1992.tb01158.x
Tsai CC, Ho YP, Chen CC (1995) Levels of interleukin-1β and interleukin-8 in gingival crevicular fluids in adult periodontitis. J Periodontol 66:852–859. https://doi.org/10.1902/jop.19126.96.36.1992
Emingil G, Çoker I, Atilla G, Hüseyinov A (2000) Levels of leukotriene B4 and platelet activating factor in gingival crevicular fluid in renal transplant patients receiving cyclosporine A. J Periodontol 71:50–57. https://doi.org/10.1902/jop.2000.71.1.50
Volin MV, Koch AE (2011) Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis. J Interf Cytokine Res 31:745–751. https://doi.org/10.1089/jir.2011.0050
Ryba-Stanisławowska M, Rybarczyk-Kapturska K, Myśliwiec M, Myśliwska J (2014) Elevated levels of serum IL-12 and IL-18 are associated with lower frequencies of CD4+ CD25 high FOXP3+ regulatory T cells in young patients with type 1 diabetes. Inflammation 37:1513–1520
Mahajani MJ, Jadhao VA, Wankhade PS, Samson E, Acharya VD, Tekale PD (2017) Effect of periodontal therapy on crevicular fluid interleukin-18 level in periodontal health and disease in Central Maharashtra (India) population. J Contemp Dent Pract 18:1085–1089. https://doi.org/10.5005/jp-journals-10024-2180
Zhang Q, Chen B, Zhu D, Yan F (2016) Biomarker levels in gingival crevicular fluid of subjects with different periodontal conditions: a cross-sectional study. Arch Oral Biol 72:92–98. https://doi.org/10.1016/j.archoralbio.2016.08.020
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the Adnan Menderes University Faculty of Dentistry Clinical Investigations Ethics Committee.
Informed consent was obtained from all of the individual participants and their parents/caregivers included in the present study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Keles, S., Anik, A., Cevik, O. et al. Gingival crevicular fluid levels of interleukin-18 and tumor necrosis factor-alpha in type 1 diabetic children with gingivitis. Clin Oral Invest (2020). https://doi.org/10.1007/s00784-020-03238-z
- Gingival crevicular fluid
- Diabetes mellitus