Primary aim of this study was to compare the local cytokine reaction associated with the clinical periodontal situation by analysing the IL-10, IL-12, IL-18 levels, and IL-18/IL-10 ratio in the GCF of subjects with stage III–IV, grade B-C periodontitis and healthy controls, and investigate any correlations between these biomarkers and clinical assessments. This evidence concerns the gene IL18 and periodontitis.