Cranberry Component Inhibition of IL-17-stimulated Cytokine Production by Gingival Cells

Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing IL-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, produced by Th17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins (PACs), which have anti-oxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of LPS- and IL-1B-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. Objectives: determine effects of IL-17 ± cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.  Methods: Cranberry high molecular weight non-dialyzable material (NDM), which is rich in PACs, was derived from cranberry juice. Smulow-Glickman (S-G) human gingival epithelial cells and normal human gingival fibroblasts were incubated with non-toxic concentrations of NDM (5-50 ug/ml), IL-17 (0.5-100 ng/ml), or NDM (2h pre-incubation) + IL-17 in serum-free medium for 6d.  IL-6 and IL-8 in culture supernatants were measured by ELISA. Data were analyzed using ANOVA and Scheffe’s F procedure for post hoc comparisons. Results: In both cell lines, IL-17 (≥ ~5-10 ng/ml) generally significantly stimulated production of IL-6 (p<0.005) and IL-8 (p<0.03). NDM inhibited constitutive IL-6 and IL-8 production by epithelial cells (p≤0.01) and fibroblasts (p≤0.03) as well as IL-17-stimulated cytokine production by epithelial cells [IL-6: maximum ~80% inhibition (p≤0.0001); IL-8: maximum ~ 70% inhibition (p≤0.03)] and fibroblasts [IL-6: maximum ~90% inhibition (p≤0.0001); IL-8: maximum ~ 80% inhibition (p≤0.008)]. Conclusions: Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by two major periodontal cell types suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis. (Supported by the University of Tennessee College of Dentistry Alumni Endowment Fund).