Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased
interleukin-18 (IL-18) levels and the pathogenesis of
chronic periodontitis, a major cause of
tooth loss. However, it has yet to be shown whether
chronic periodontitis results from or causes an increase in
IL-18 after
bacterial infection. In the present study, we investigated how
IL-18 overexpression relates to
periodontal disease using
IL-18 transgenic (Tg) mice. IL-18Tg and wild-type mice were inoculated intraorally with Porphyromonas (P.) gingivalis, which has been implicated in the etiology of
chronic periodontitis. Seventy days after P. gingivalis
infection,
alveolar bone loss and gingival
cytokine levels were assessed using histo-morphological analysis and
enzyme-linked immuno-absorbent assay, respectively.
Periodontal bone loss was evoked in IL-18Tg mice, but not in wild-type mice. Interestingly, levels of bone-resorptive
cytokines, including IL-1α, IL-1β,
tumor necrosis factor-α, and
IL-6, were unchanged in the gingival tissues of IL-18Tg mice infected with P. gingivalis, although levels of
interferon γ (a proinflammatory T-helper 1
cytokine) decreased. RT-PCR analysis showed elevated expression of mRNAs for
receptor activator of nuclear factor kappa-B ligand (a key stimulator of osteoclast development and activation) and
CD40 ligand (a marker of T cell activation) in the gingiva of IL-18Tg mice infected with P. gingivalis. We conclude that increased
IL-18 in the gingival tissues evokes
chronic periodontitis after
bacterial infection, presumably via a T cell-mediated pathway.