Cytokine response in periimplantitis

Dental implants are widely used in current dentistry and effectively replace the lost teeth. However, due to concomitant risk factors and low oral immunity, the patients develop peri-implantitis (PI), accompanied by inflammation and general immune response. Meanwhile, the local cytokine profile in saliva remains insufficiently studied. The purpose of this study was to assess cytokine response and evaluate the diagnostic information content of proand anti-inflammatory cytokines in patients with PI. We have examined sixty-five patients with PI aged 50-65 years and 48 PI-free patients aged 50-65 years. The PI diagnosis was carried out based on the results of clinical examination, presence of symptoms, i.e., bleeding during probing, suppuration during probing, bone loss on radiographs ≥ 3 mm, and the depth of the gingival pocket ≥ 6 mm. In saliva samples collected in the morning on rest, the content of several proand anti-inflammatory cytokines was determined by enzyme immunoassay (ELISA) using Protein Contour kits (St. Petersburg). The cytokine profile of patients with PI is characterized by expression of both pro-inflammatory and anti-inflammatory cytokines. The salivary content of IL-1 increased, particularly, among patients with PI (205.9±4.2 pg/mL versus 67.5±3.1 pg/mL in participants without peri-implantitis). IL-6 levels were increased to 29.4±1.3pg/mL versus 11.7±1.2 pg/mL, respectively, showing a significant difference for the both parameters. In addition, the level of IL-19 increased to 54.9±2.3 pg/mL against the comparison group (30.5±1.4 pg/mL); TNFα, to 202.4±3.8 pg/mL compared to 115.6±2.4 pg/mL, respectively (p < 0.001). Moreover, the salivary concentration of IL-4 was significantly increased in patients with PI (18.2±1.4 pg/mL versus 3.8±0.6 pg/mL in comparison group), along with higher IL-10 amounts (66.5±2.7 pg/mL versus 15.3±0.9 pg/mL, respectively, p < 0,001). An estimation by the Kullback information measure revealed the highest diagnostic information content for IL-4 (8.5), IL-10 (8.1), IL-1β (5.7), IL-6 (4.2). To justify the diagnostic criteria, one may recommend usage of IL-4, IL-10, IL-1β and IL-6 levels established in saliva.

1. Agarkov N.M., Lev I.V., Tanygin M.O., Korovin E.N. Social functional activity of patients with diabetic retinopathy. Nauchnye rezultaty biomeditsinskikh issledovaniy = Research Results in Biomedicine, 2022, Vol. 8, no. 4, pp. 516-523. (In Russ.)

2. Derks J., Tomasi C. Peri-implant health and disease. A systematic review of current epidemiology. J. Clin. Periodontol., 2015, Vol. 42, Suppl. 16, pp. S158-S171.

3. He K., Jian F., He T., Tang H., Huang B., Wei N. Analysis of the association of TNF-α, IL-1A, and IL-1B polymorphisms with peri-implantitis in a Chinese non-smoking population. Clin. Oral Investig., 2020, Vol. 24, no. 2, pp. 693-699.

4. Khammissa R.A., Feller L., Meyerov R., Lemmer J. Peri-implant mucositis and peri-implantitis: clinical and histopathological characteristics and treatment. SADJ, 2012, Vol. 67, no. 3, pp. 122-126.

5. Lee C.T., Huang Y.W., Zhu L., Weltman R. Prevalences of peri-implantitis and peri-implant mucositis: systematic review and meta-analysis. J. Dent., 2017, Vol. 62, pp. 1-12.

6. Malmqvist S., Clark R., Johannsen G., Johannsen A., Boström E.A., Lira-Junior R. Immune cell composition and inflammatory profile of human peri-implantitis and periodontitis lesions. Clin. Exp. Immunol., 2024, Vol. 217, no. 2, pp. 173-182.

7. Naugler W.E., Sakurai T., Kim S., Maeda S., Kim K., Elsharkawy A.M., Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science, 2007, Vol. 317, no. 5834, pp. 121-124.

8. Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int. J. Biol. Sci., 2012, Vol. 8, no. 9, pp. 1237-1247.

9. Salvi G.E., Cosgarea R., Sculean A. Prevalence of periimplant diseases. Implant Dent., 2019, Vol. 28, no. 2, pp. 100-102.

10. Saremi L., Shafizadeh M., Esmaeilzadeh E., Ghaffari M.E., Mahdavi M.H., Amid R., Kadkhodazadeh M. Assessment of IL-10, IL-1ß and TNF-α gene polymorphisms in patients with peri-implantitis and healthy controls. Mol. Biol. Rep., 2021, Vol. 48, no. 3, pp. 2285-2290.

11. Saxena A., Rastogi P.K., Lal N., Verma U.P., Singhal R., Ahmad M.K. Evaluating the role of inflammatory biomarkers as a diagnostic tool in peri-implantitis. J. Oral Biol. Craniofac. Res., 2025, Vol. 15, no. 2, pp. 228-233.

12. Simonis P., Dufour T., Tenenbaum H. Long-term implant survival and success: a 10-16-year follow-up of non-submerged dental implants. Clin. Oral Implants Res., 2010, Vol. 21, no. 7, 772-777.