ROLE OF PRO- AND ANTI-INFLAMMATORY INTERLEUKINS IN PERIODONTITIS: MOLECULAR, IMMUNOLOGICAL, AND THERAPEUTIC SIGNIFICANCE

Natasza Jankowska; Marta Krzyżanowska; Agata Wnęk; Zuzanna Hucała; Natalia Dymel; Weronika Jagiełło; Natalia Le-Hong; Alicja  Biskup

doi:10.31435/ijitss.3(51).2026.6281

Authors

Natasza Jankowska Specialized Dental Clinic, 5th Military Clinical Hospital with Polyclinic- Independent Public Healthcare Institution, Krakow, Poland https://orcid.org/0009-0009-0491-3716
Marta Krzyżanowska Mix-Med Arima Private Healthcare Institution, Radom, Poland https://orcid.org/0009-0001-2932-0337
Agata Wnęk Specialized Dental Clinic, 5th Military Clinical Hospital with Polyclinic - Independent Public Healthcare Institution, Krakow, Poland https://orcid.org/0009-0004-5384-4597
Zuzanna Hucała Specialized Dental Clinic, 5th Military Clinical Hospital with Polyclinic - Independent Public Healthcare Institution, Krakow, Poland https://orcid.org/0009-0005-4859-1406
Natalia Dymel Specialized Dental Clinic, 5th Military Clinical Hospital with Polyclinic - Independent Public Healthcare Institution, Krakow, Poland https://orcid.org/0009-0009-3928-5393
Weronika Jagiełło 5th Military Clinical Hospital with Polyclinic - Independent Public Healthcare Institution, Krakow, Poland https://orcid.org/0009-0000-5200-9208
Natalia Le-Hong 5th Military Clinical Hospital with Polyclinic - Independent Public Healthcare Institution, Krakow, Poland https://orcid.org/0009-0000-0540-8222
Alicja Biskup University Dental Centre of the Silesian Medical University in Katowice, sp. z o.o., Bytom, Poland https://orcid.org/0009-0001-2228-1478

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6281

Keywords:

Periodontitis, Interleukins, IL-1β, IL-6, IL-17, IL-10, Periodontal Immunology

Abstract

Periodontitis is a chronic, biofilm-associated inflammatory disease in which tissue destruction reflects an altered host immune response more than the direct action of bacteria alone. This structured narrative review examines the molecular, immunological, diagnostic, and therapeutic significance of pro- and anti-inflammatory interleukins in periodontitis. A targeted literature search was performed in PubMed/MEDLINE, PubMed Central, Scopus, Web of Science, and Google Scholar for English-language publications from 2016 to 2026. Search terms combined 'periodontitis,' 'periodontal disease,' 'interleukin,' 'cytokine,' 'IL-1β,' 'IL-6,' 'IL-10,' 'IL-17,' 'IL-23,' 'IL-33,' 'IL-35,' 'IL-38,' 'inflammasome,' 'saliva,' and 'gingival crevicular fluid.' In the expanded search, 106 records were screened by title and abstract, 53 full-text papers were assessed, and 35 peer-reviewed publications were selected because they directly addressed interleukin expression, signaling, biomarker value, genetic variation, or therapeutic modulation in periodontal disease. Overall, IL-1β and IL-6 remain the most consistent salivary and gingival crevicular fluid biomarkers of disease severity. The IL-23/IL-17 pathway links adaptive immunity with neutrophil recruitment, RANKL expression, and osteoclastogenesis, whereas IL-10, IL-35, and IL-38 illustrate the importance of regulatory cytokine networks. Interleukin-directed therapy is not yet ready for routine periodontal use, but local, phenotype-guided immunomodulation may become a rational adjunct to conventional periodontal treatment.

References

Papapanou, P. N., Sanz, M., Buduneli, N., Dietrich, T., Feres, M., Fine, D. H., Flemmig, T. F., Garcia, R., Giannobile, W. V., Graziani, F., Greenwell, H., Herrera, D., Kao, R. T., Kebschull, M., Kinane, D. F., Kirkwood, K. L., Kocher, T., Kornman, K. S., Kumar, P. S., ... Tonetti, M. S. (2018). Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Journal of Clinical Periodontology, 45(Suppl. 20), S162–S170. https://doi.org/10.1111/jcpe.12946

Van Dyke, T. E., Bartold, P. M., & Reynolds, E. C. (2020). The nexus between periodontal inflammation and dysbiosis. Frontiers in Immunology, 11, 511. https://doi.org/10.3389/fimmu.2020.00511

Neurath, N., & Kesting, M. (2024). Cytokines in gingivitis and periodontitis: From pathogenesis to therapeutic targets. Frontiers in Immunology, 15, 1435054. https://doi.org/10.3389/fimmu.2024.1435054

Martínez-García, M., & Hernández-Lemus, E. (2025). Pro-inflammatory and anti-inflammatory interleukins in periodontitis: Molecular roles, immune crosstalk, and therapeutic perspectives. International Journal of Molecular Sciences, 26(20), 10094. https://doi.org/10.3390/ijms262010094

Stadler, A. F., Angst, P. D. M., Arce, R. M., Gomes, S. C., Oppermann, R. V., & Susin, C. (2016). Gingival crevicular fluid levels of cytokines/chemokines in chronic periodontitis: A meta-analysis. Journal of Clinical Periodontology, 43(9), 727–745. https://doi.org/10.1111/jcpe.12557

Relvas, M., Mendes-Frias, A., Gonçalves, M., Salazar, F., López-Jarana, P., Silvestre, R., & Viana da Costa, A. (2024). Salivary IL-1β, IL-6, and IL-10 are key biomarkers of periodontitis severity. International Journal of Molecular Sciences, 25(15), 8401. https://doi.org/10.3390/ijms25158401

Arroyo, E., Oliveira-Alves, M. G., Chamorro-Petronacci, C. M., Marichalar-Mendia, X., Bravo-López, S. B., Blanco-Carrión, J., & Pérez-Sayáns, M. (2023). Protein-based salivary biomarkers for the diagnosis of periodontal diseases: Systematic review and meta-analysis. Journal of Taibah University Medical Sciences, 18(4), 737–747. https://doi.org/10.1016/j.jtumed.2022.12.004

Marchesan, J. T., Girnary, M. S., Moss, K., Monaghan, E. T., Egnatz, G. J., Jiao, Y., et al. (2020). Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics. Periodontology 2000, 82(1), 93–114. https://doi.org/10.1111/prd.12269

Murakami, T., Takahata, Y., Hata, K., & Nishimura, R. (2020). Role of interleukin-1 and inflammasomes in oral disease. Journal of Oral Biosciences, 62(3), 242–248. https://doi.org/10.1016/j.job.2020.07.003

Bonsmann, T., Mochol, M., Bonsmann, E., Jablonowski, L., Pawlik, A., Rasławska-Socha, J., Lipski, M., & Mazurek-Mochol, M. (2025). The role of IL-17 in periodontitis and its systemic connections. International Journal of Molecular Sciences, 26(22), 10902. https://doi.org/10.3390/ijms262210902

Zhang, J., Ding, Q., Wang, A. X., Lin, M., Yu, N., Moss, K., Williamson, M. A., Miao, D., Marchesan, J. T., Zeng, E., Shi, W., Sun, H., Lei, Y. L., & Zhang, S. (2025). Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis. Life Sciences, 371, 123559. https://doi.org/10.1016/j.lfs.2025.123559

Papathanasiou, E., Conti, P., Carinci, F., Lauritano, D., & Theoharides, T. C. (2020). IL-1 superfamily members and periodontal diseases. Journal of Dental Research, 99(13), 1425–1434. https://doi.org/10.1177/0022034520945209

Alarcón-Sánchez, M. A., Rodríguez-Montaño, R., Mosaddad, S. A., & Heboyan, A. (2025). Levels of IL-1β, MMP-8, and MMP-9 in the saliva of subjects with periodontitis: A systematic review and meta-analysis. Journal of Clinical Laboratory Analysis, 39(10), e70040. https://doi.org/10.1002/jcla.70040

Marchesan, J. T. (2020). Inflammasomes as contributors to periodontal disease. Journal of Periodontology, 91(Suppl. 1), S6–S11. https://doi.org/10.1002/JPER.20-0157

Karrabi, M., Baghani, Z., & Atarbashi-Moghadam, F. (2024). Effect of adjunctive photodynamic therapy on gingival crevicular fluid interleukin-1β in stage III and IV periodontitis: A systematic review and meta-analysis. Journal of Indian Society of Periodontology, 28(2), 156–175. https://doi.org/10.4103/jisp.jisp_494_23

Gomes, P.-R., Rocha, M.-D., Lira, J.-A., Coelho, F.-A., Alves, E.-H., Nascimento, H.-M., Oliveira, S.-M., Carmo, R.-R., Araújo, H.-T., Silva, F.-R., & Vasconcelos, D.-F. (2023). Salivary biomarkers present in patients with periodontitis without clinical distinction: Findings from a meta-analysis. Medicina Oral, Patología Oral y Cirugía Bucal, 28(5), e457–e466. https://doi.org/10.4317/medoral.25876

Mazurek-Mochol, M., Bonsmann, T., Mochol, M., Poniewierska-Baran, A., & Pawlik, A. (2024). The role of interleukin 6 in periodontitis and its complications. International Journal of Molecular Sciences, 25(4), 2146. https://doi.org/10.3390/ijms25042146

Martins, A. A., Lima, M. L. S., Vieira, G. H. A., Costa, H. E. S., Leitão, R. F. C., Ribeiro, S. B., Medeiros, C. A. C. X., Silva, D. N. A., Suksakulchai, R., Pirih, F. Q., Brito, G. A. C., Garcia, V. B., Araújo Júnior, R. F., Lins, R. D. A. U., & Araújo, A. A. (2025). Effectiveness of local tocilizumab administration in mitigating alveolar bone loss and inflammation in experimental periodontitis. Scientific Reports, 16(1), 1004. https://doi.org/10.1038/s41598-025-30737-4

Rodríguez-Montaño, R., Alarcón-Sánchez, M. A., Lomelí-Martínez, S. M., Martínez-Bugarin, C. H., & Heboyan, A. (2025). Genetic variants of the IL-23/IL-17 axis and its association with periodontal disease: A systematic review. Immunity, Inflammation and Disease, 13(2), e70147. https://doi.org/10.1002/iid3.70147

Liukkonen, J., Gürsoy, U. K., Pussinen, P. J., Suominen, A. L., & Könönen, E. (2016). Salivary concentrations of interleukin (IL)-1β, IL-17A, and IL-23 vary in relation to periodontal status. Journal of Periodontology, 87(12), 1484–1491. https://doi.org/10.1902/jop.2016.160146

Sasikumar, P. K., Varghese, S. S., Kumaran, T., & Devi, S. S. (2020). Meta-analysis of risk association between interleukin-17A gene polymorphism and chronic periodontitis. Contemporary Clinical Dentistry, 11(1), 3–9. https://doi.org/10.4103/ccd.ccd_448_19

Alarcón-Sánchez, M. A., Romero-Castro, N. S., Becerra-Ruiz, J. S., Romero-Servin, S., & Heboyan, A. (2024). Increased of IL-18 levels are associated with periodontitis: A systematic review and meta-analysis. BMC Oral Health, 24, 981. https://doi.org/10.1186/s12903-024-04747-z

Alarcón-Sánchez, M. A., Romero-Castro, N. S., Reyes-Fernández, S., Sánchez-Tecolapa, E. U., & Heboyan, A. (2024). Expression of IL-33 in subjects with periodontitis: A systematic review and meta-analysis. European Journal of Medical Research, 29, 440. https://doi.org/10.1186/s40001-024-02039-4

Liu, A., Hayashi, M., Ohsugi, Y., Katagiri, S., Akira, S., Iwata, T., & Nakashima, T. (2024). The IL-33/ST2 axis is protective against acute inflammation during the course of periodontitis. Nature Communications, 15, 2707. https://doi.org/10.1038/s41467-024-46746-2

Yang, S.-L., & Huang, S.-J. (2019). Interleukin-10 polymorphisms (rs1800871, rs1800872 and rs1800896) and periodontitis risk: A meta-analysis. Archives of Oral Biology, 97, 59–66. https://doi.org/10.1016/j.archoralbio.2018.10.012

Skrypnyk, M., Spahr, A., Berkovsky, S., Yatsenko, T., Xu, C., Zuieva, O., Osada, T., Takahashi, S., Hattori, N., Takahashi, K., Hattori, K., & Heissig, B. (2025). Chronic stress and the IL-10-mediated immunoregulatory loop in the pathogenesis of periodontitis. Clinical Science, 139(22), 1469–1487. https://doi.org/10.1042/CS20256843

Yue, G., Qian, J., Weng, B., Mao, J., Zhang, M., Wang, S., & Huang, W. (2025). Effect of scaling and root planing on TNF-α, IL-1β, and IL-10 levels in periodontitis patients with and without diabetes: A cross-sectional study. BMC Oral Health, 25, 1481. https://doi.org/10.1186/s12903-025-06894-3

Chen, D., Zhang, T.-L., & Wang, X. (2016). Association between polymorphisms in interleukins 4 and 13 genes and chronic periodontitis in a Han Chinese population. BioMed Research International, 2016, 8389020. https://doi.org/10.1155/2016/8389020

Schmidlin, P. R., Dehghannejad, M., & Fakheran, O. (2021). Interleukin-35 pathobiology in periodontal disease: A systematic scoping review. BMC Oral Health, 21, 139. https://doi.org/10.1186/s12903-021-01515-1

Pashova-Tasseva, Z., Mlachkova, A., Kotsilkov, K., & Maynalovska, H. (2025). The multifaceted role of IL-35 in periodontal disease and beyond: From genetic polymorphisms to biomarker potential. Genes, 16(8), 891. https://doi.org/10.3390/genes16080891

Toraman, A., Sağlam, E., Savran, L., & Köseoğlu, S. (2025). Evaluation of salivary IL-38 levels in periodontitis: A cross-sectional study. Journal of Interferon & Cytokine Research, 45(2), 76–82. https://doi.org/10.1089/jir.2023.0233

Jaedicke, K. M., Preshaw, P. M., & Taylor, J. J. (2016). Salivary cytokines as biomarkers of periodontal diseases. Periodontology 2000, 70(1), 164–183. https://doi.org/10.1111/prd.12117

Suvan, J., Leira, Y., Moreno Sancho, F. M., Graziani, F., Derks, J., & Tomasi, C. (2020). Subgingival instrumentation for treatment of periodontitis: A systematic review. Journal of Clinical Periodontology, 47(Suppl. 22), 155–175. https://doi.org/10.1111/jcpe.13245

Ho, S. N., Acharya, A., Sidharthan, S., Li, K. Y., Leung, W. K., McGrath, C., & Pelekos, G. (2020). A systematic review and meta-analysis of clinical, immunological, and microbiological shift in periodontitis after nonsurgical periodontal therapy with adjunctive use of probiotics. Journal of Evidence-Based Dental Practice, 20(1), 101397. https://doi.org/10.1016/j.jebdp.2020.101397

Kruse, A. B., Kowalski, C. D., Leuthold, S., Vach, K., Ratka-Krüger, P., & Woelber, J. P. (2020). What is the impact of the adjunctive use of omega-3 fatty acids in the treatment of periodontitis? A systematic review and meta-analysis. Lipids in Health and Disease, 19, 100. https://doi.org/10.1186/s12944-020-01267-x