Salivary Cytokine Profiles in Active Smokers: An Exploratory Cross-Sectional Study of IL-2, IL-6, and IL-8

Background: Active smoking is recognized as a major risk factor for oral and systemic inflammatory disorders. Tobacco smoke can alter immune responses and modulate the production of pro-inflammatory cytokines, potentially contributing to periodontal tissue damage and impaired oral health. Salivary biomarkers represent a non-invasive and clinically accessible approach for monitoring inflammatory processes. The present study aimed to evaluate salivary levels of interleukin-2 (IL-2), interleukin-6 (IL-6), and interleukin-8 (IL-8) in active smokers and non-smokers and to explore their potential relevance as indicators of oral inflammatory status. Methods: A total of 98 clinically healthy adults aged 20-72 years were included in this cross-sectional study. Participants were divided into four groups according to smoking status and sex: female controls, male controls, female smokers, and male smokers. Unstimulated saliva samples were collected using standardized procedures and analyzed for IL-2, IL-6, and IL-8 concentrations using commercially available ELISA kits. Statistical analyses were performed using SPSS, with significance set at p < 0.05. Results: Salivary cytokine profiles differed between smokers and non-smokers across all investigated biomarkers. Female smokers exhibited lower mean IL-8 levels than female controls, whereas male smokers showed slightly lower IL-8 concentrations than male controls. IL-6 concentrations tended to be higher in female smokers and lower in male smokers relative to their respective control groups. Similarly, IL-2 levels displayed modest variations between smokers and non-smokers. However, none of the observed differences were statistically significant (p > 0.05). A significant positive correlation was identified between salivary IL-2 and IL-6 concentrations (r = 0.559, p < 0.001). Conclusions: Although statistically significant differences were not identified, the observed trends suggest that active smoking may influence salivary cytokine profiles associated with oral inflammatory responses. Salivary IL-2, IL-6, and IL-8 remain promising biomarkers for the non-invasive assessment of inflammatory status and warrant further investigation in larger cohorts. Future studies incorporating additional clinical and periodontal parameters are needed to clarify the relationship between smoking-related immune modulation and oral inflammatory processes.