Impact of smoking and periodontitis on salivary IL-39, IL-41, IL-1β, and TNF-α levels: a cross-sectional analysis.

BACKGROUND

This study investigated the effects of periodontitis and smoking on salivary interleukin (IL)-39, IL-41, IL-1β, and tumor necrosis factor-alpha (TNF-α) levels. IL-39 and IL-41 are recently identified cytokines whose roles in periodontal inflammation remain largely unexplored. Clarifying their salivary profiles may provide new, non-invasive biomarkers for disease activity and tobacco-related modulation of the host immune response.

METHODS

88 participants were classified into four groups based on periodontal and smoking status. Unstimulated saliva samples were collected and analyzed for IL-39, IL-41, IL-1β, and TNF-α levels using ELISA. Clinical periodontal parameters were recorded, correlations between salivary cytokine levels and clinical parameters were assessed, and receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic accuracy.

RESULTS

Periodontitis patients exhibited significantly higher salivary IL-39, IL-1β, and TNF-α levels compared with periodontally healthy individuals (p < 0.001), whereas IL-41 showed no significant differences among groups. IL-39 and TNF-α demonstrated the strongest correlations with clinical periodontal parameters. ROC analysis revealed that IL-39 had the highest diagnostic accuracy for distinguishing periodontitis from health in both smokers (AUC = 0.861) and non-smokers (AUC = 0.808), while the diagnostic capacity of IL-1β was impaired in smokers.

CONCLUSIONS

Salivary IL-39 and TNF-α emerged as the most reliable biomarkers for distinguishing periodontitis from health, whereas IL-1β showed reduced diagnostic accuracy in smokers and IL-41 provided limited utility. These findings indicate that smoking primarily modulates the diagnostic performance rather than the absolute levels of salivary cytokines.

TRIAL REGISTRATION: The current study was registered at ClinicalTrials.gov (NCT06528522) on July 12, 2024.