Interleukin-18 concentrations and the pathogenesis of periodontal disease

Background: Interleukin-18 (IL-18) is reported as an important regulatory cytokine in non-oral inflammation. Our objective was to compare the concentrations of IL-18 within diseased and healthy human gingiva with concentrations of other TO and T(H)2 cytokines to determine possible effects of IL-18 on gingival inflammation. Methods: Gingival biopsies were obtained prior to routine tooth extraction. Gingiva was grouped by the depth of the adjacent gingival sulcus: <= 3 healthy (featuring no bleeding on probing) and >= 3 mm diseased (featuring bleeding on probing). Diseased gingiva was subdivided into 3, 4 to 6 and > 6 mm groups. Gingival interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-18, and interferon (IFN)-gamma concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). Data were compared by factorial analysis of variance and the Pearson's correlation test. Results: Concentrations of IL-2, IL-4 IL-6, IL-10, IL-18, and IFN-gamma adjacent to 4 to 6 mm diseased sites were greater than adjacent to <= 3 mm healthy sites (P < 0.001). IL-12 concentrations were lower within diseased than within healthy gingiva (P < 0.001). IL-6 and IL-18 concentrations were greater adjacent to > 6 mm sites compared to healthy sites (P < 0.001); the concentrations of the other cytokines (except IL-12) were similar to healthy sites. IL-6 and IL-18 concentrations were positively correlated, and IFN-gamma and IL-12 negatively correlated, with the adjacent gingival sulcular depth. Conclusions: Periodontal inflammation may not successfully resolve because of accumulation of IL-6 and IL-18, and decreased concentrations of IL-12, within diseased gingiva. Because of the highly significant correlation between IL-18 concentration and gingival sulcular depth, IL-18 may be a useful target for either preventive or palliative therapy for periodontitis.