Evaluation Of IL-6 And IL-8 In the Saliva of Patients with Type II Diabetes Mellitus After Tooth Extraction

Abstract

Type II diabetes mellitus (T2DM) is characterized by chronic low-grade inflammation and impaired wound healing, which may have undesirable effects on the outcomes of oral surgery. The expression of proinflammatory cytokines, including IL-6 and IL-8, is fundamental in immune regulation and for tissue damage or recovery. The purpose of the present investigation was to measure salivary IL-6 and IL-8 in patients with type II diabetes mellitus before and after undergoing tooth extraction, as well as in a control group of systemically healthy individuals. This was an observational case–control study that was performed at the college of dentistry university of Kufa, Al-Najaf, Iraq from April 2025 to December 2025. Sixty individuals participated in the study, including 30 T2DM patients and 30 gender- and age-matched healthy controls. Unstimulated whole saliva was collected one hour before extraction and two days after extraction. Enzyme linked immunosorbent assay (ELISA) was used to determine the levels of IL-6 and IL-8 in saliva. The statistical analysis between the two groups was analyzed by independent-samples and paired t-test with P < 0.05 considered as significant. At baseline, the concentrations of salivary IL-6 and IL-8 was significantly higher in patients with T2DM compared to controls (P < 0.05). Both cytokines were significantly elevated (P < 0.001) when compared with the basal values in diabetics on day 2 following tooth extraction; this difference was still statistically significant from that observed in controls (P < 0.05). Type II diabetes mellitus patients have a high salivary level of IL-6 and IL-8 at the baseline and an exaggerated response to inflammation after tooth extraction. These results indicate that diabetic patients have a chronic inflammatory phase, which might affect the ability to heal wounds. Salivary IL-6 and IL-8 can be potentially useful, non-invasive biomarkers for monitoring POI in T2DM patients.

Keywords:

Interleukin-6, Interleukin-8, Tooth Extraction, Saliva, BOP, PI, GI

References

Adnan, S. B., Maarof, M., Fauzi, M. B., & Md Fadilah, N. I. (2025). Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense. International Journal of Molecular Sciences, 26(13), 5920. https://doi.org/10.3390/ijms26135920

Al Shehhi, Y. I., Elemam, N. M., & Alsaegh, M. A. (2024). The response of salivary proinflammatory biomarkers to tooth extraction in individuals with type II diabetes mellitus. BMC oral health, 24(1), 250. https://doi.org/10.1186/s12903-024-04006-1

American Diabetes Association Professional Practice Committee (2025). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes care, 48(1 Suppl 1), S181–S206. https://doi.org/10.2337/dc25-S009

Asoka, S., Panneerselvam, E., Pandya, A. R., Raja, V. B. K., & Ravi, P. (2022). Effect of platelet-rich fibrin on extraction socket healing in diabetic patients - A split-mouth crossover study: A prospective clinical trial. National journal of maxillofacial surgery, 13(1), 39–43. https://doi.org/10.4103/njms.njms_422_21

Babadi,F. (2020). Salivary and Serum Levels of IL-6 and IL-8 in Diabetic Patients with Periodontal Disease: A Review Article. Jundishapur Journal of Health Sciences, 12(2), 17-22. doi: https://doi.org/10.5812/jjhs.101051

Cenzato, N., Cazzaniga, F., Maspero, C., Tartaglia, G. M., & Del Fabbro, M. (2023). SALIVA-based diagnostic approach for diabetes mellitus: a step towards non-invasive detection - a scoping review. European review for medical and pharmacological sciences, 27(24), 12080–12087. https://doi.org/10.26355/eurrev_202312_34806

Costa, P. P., Trevisan, G. L., Macedo, G. O., Palioto, D. B., Souza, S. L., Grisi, M. F., Novaes, A. B., Jr, & Taba, M., Jr (2010). Salivary interleukin-6, matrix metalloproteinase-8, and osteoprotegerin in patients with periodontitis and diabetes. Journal of periodontology, 81(3), 384–391. https://doi.org/10.1902/jop.2009.090510

Harada, A., Sekido, N., Akahoshi, T., Wada, T., Mukaida, N., & Matsushima, K. (1994). Essential involvement of interleukin-8 (IL-8) in acute inflammation. Journal of leukocyte biology, 56(5), 559–564.

Hotamisligil G. S. (2017). Inflammation, metaflammation and immunometabolic disorders. Nature, 542(7640), 177–185. https://doi.org/10.1038/nature21363

Injeyan, H. S., Teodorczyk-Injeyan, J. A., Hogg-Johnson, S., Rashed, S., Lee, J., & Harris, G. (2025). Salivary Biomarkers of Inflammation in Patients With Chronic Non-Specific Low Back Pain. Biomarker insights, 20, 11772719251355038. https://doi.org/10.1177/11772719251355038

Ko, K. I., Sculean, A., & Graves, D. T. (2021). Diabetic wound healing in soft and hard oral tissues. Translational research : the journal of laboratory and clinical medicine, 236, 72–86. https://doi.org/10.1016/j.trsl.2021.05.001

Orzechowska-Wylęgała, B., Wylęgała, A., Fiolka, J. Z., Czuba, Z., Kryszan, K., & Toborek, M. (2024). Selected Saliva-Derived Cytokines and Growth Factors Are Elevated in Pediatric Dentofacial Inflammation. International Journal of Molecular Sciences, 25(16), 8680. https://doi.org/10.3390/ijms25168680

Preshaw, P. M., Alba, A. L., Herrera, D., Jepsen, S., Konstantinidis, A., Makrilakis, K., & Taylor, R. (2012). Periodontitis and diabetes: a two-way relationship. Diabetologia, 55(1), 21–31. https://doi.org/10.1007/s00125-011-2342-y

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

Sahibzada, H. A., Khurshid, Z., Khan, R. S., Naseem, M., Siddique, K. M., Mali, M., & Zafar, M. S. (2017). Salivary IL-8, IL-6 and TNF-α as Potential Diagnostic Biomarkers for Oral Cancer. Diagnostics (Basel, Switzerland), 7(2), 21. https://doi.org/10.3390/diagnostics7020021

Saim, F. I., Sjamsudin, E., & Najmi, N. (2025). The Role of Inflammatory Biomarkers (IL-1, IL-6, TNF-α, and Alpha-Amylase) in Saliva on Post-Odontectomy Swelling: A Rapid Review. Journal of inflammation research, 18, 12227–12243. https://doi.org/10.2147/JIR.S536809

Sangappa, S. B., Babu, H. M., Savadi, R. C., Krishnamurthy, P. T., & Ravi Kiran, A. V. V. V. (2024). Salivary Interleukin-6 as a Non-Invasive Biomarker for Chronic Periodontitis and Tooth Loss in Type 2 Diabetes. Indian journal of dental research : official publication of Indian Society for Dental Research, 35(1), 28–33. https://doi.org/10.4103/ijdr.ijdr_112_23

Shirzaiy, M., Dalirsani, Z., Peymankar, P., & Taherizadeh, M. (2023). Relationship between salivary levels of interleukin-8 and HbA1c in patients with type 2 diabetes. Endocrinology, diabetes & metabolism, 6(6), e455. https://doi.org/10.1002/edm2.455

Tanaka, T., Narazaki, M., & Kishimoto, T. (2016). Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy, 8(8), 959–970. https://doi.org/10.2217/imt-2016-0020

Thimmappa, P. Y., Vasishta, S., Ganesh, K., Nair, A. S., & Joshi, M. B. (2023). Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections. Human cell, 36(4), 1265–1282. https://doi.org/10.1007/s13577-023-00905-7