Salivary Cortisol and Periodontitis Severity: A Cross-Sectional Biomarker-Based Assessment of Stress and Inflammation

<b>Background:</b> Psychological stress is increasingly recognized as a potential modifier of periodontal disease through both behavioral and biological mechanisms. Cortisol, a key stress hormone, exerts complex immunomodulatory effects and may influence periodontal inflammation and tissue breakdown. This study aimed to compare salivary levels of cortisol, interleukin-1β, and interleukin-6 in patients with varying periodontitis severity and examine their associations with clinical periodontal parameters. <b>Methods:</b> A total of 67 patients diagnosed with periodontitis were classified according to the 2017 World Workshop Classification into Stage I/II vs. Stage III/IV and Grade B vs. Grade C. Unstimulated saliva samples were collected and analyzed for cortisol using electrochemiluminescence immunoassay, and for IL-1β and IL-6 using ELISA. Statistical analyses included Mann-Whitney U test, Spearman's correlations, and multivariate regression. <b>Results:</b> Median salivary cortisol levels were significantly higher in Stage III/IV (11.90 nmol/L) than in Stage I/II (7.64 nmol/L; <i>p</i> = 0.014) and in Grade C (10.60 nmol/L) vs. Grade B (7.70 nmol/L; <i>p</i> = 0.019). In multivariate analysis, cortisol independently predicted both Stage III/IV (OR = 1.23, <i>p</i> = 0.007) and Grade C (OR = 1.24, <i>p</i> = 0.026) periodontitis. ROC analysis showed that salivary cortisol had moderate diagnostic performance for Stage III/IV periodontitis (AUC = 0.68, cut-off 11.57 nmol/L) and Grade C (AUC = 0.67, cut-off 9.76 nmol/L). Cortisol showed significant positive correlations with clinical markers of disease severity and with IL-1β (r = 0.399, <i>p</i> = 0.001) and IL-6 (r = 0.424, <i>p</i> < 0.001). <b>Conclusions:</b> Salivary cortisol is a promising non-invasive biomarker reflecting both stress-related physiological burden and clinical severity in periodontitis. Cortisol measurement may represent a valuable addition to multifactorial assessments and risk stratification in periodontitis, pending further validation in longitudinal studies.