Interferon gamma (IFN- g) is an important inflammatory cytokine in periodontitis and it is known that the production of IFN-g is regulated by IL-18 (and IL-12) from myeloid immune cells. Stimulation of monocytes with E.coli lipopolysaccharide (LPS) induces production of IL-18 and the activity of IL-18 is strictly controlled by IL-18 binding protein A (IL-18BPa) since over-production of the cytokine may result in exaggerated release of IFN-g and subsequent tissue pathology. Objective: To examine the relationship between IL-18 and IL-18BPa in human THP1 monocytes stimulated with P. gingivalis LPS. Methods: Cells from the pro-monocyte cell line THP-1 were treated with Vitamin D3 (0.1 µM) to induce differentiation into monocyte-like cells. THP-1 monocytes were cultured with LPS from P. gingivalis strain W50 (100 ng/ml) for 6 hours. In blocking experiments cells were pre-incubated with IL-18BPa monoclonal antibody. IL-18 and IL-18BPa were measured in the culture supernatants by ELISA and Western blotting. Results: THP1 cells produce significant (p< 0.05) amounts of IL-18 and IL-18 BPa within 6h of stimulation with P.gingivalis LPS. Furthermore, IL-18 can be significantly increased in a dose dependent manner by the addition of anti-IL-18BPa, thus indicating that IL-18BPa produced within 6h post-stimulation may have a suppressive effect on IL-18 induced by P. gingivalis LPS. Conclusions: The results indicate that IL-18/IL-18BPa balance may be important in the maintenance of steady state conditions and the development of periodontal pathology. Supported by the Oral and Dental Trust UK and Department of Health UK.

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