IL-1 AND TNF ANTAGONISTS INHIBIT THE INFLAMMATORY RESPONSE AND BONE LOSS IN EXPERIMENTAL PERIODONTITIS

Periodontal disease is the most frequent cause of tooth loss in humans and is the most prevalent disease associated with bone loss, includin g osteoporosis. Periodontal destruction is initiated by bacteria that colonize the tooth surface, leading to inflammation and bone resorptio n. To assess the roles of IL-1 and TNF in this process, studies were c onducted in a Macaca fascicularis primate model of experimental period ontitis. Function-blocking soluble receptors to IL-1 and TNF were appl ied by local injection to sites with induced periodontal destruction a nd compared with similar sites injected with vehicle alone. The result s indicate that injection of soluble receptors to IL-1 and TNF inhibit ed by approximately 80% the recruitment of inflammatory cells in close proximity to bone. The formation of osteoclasts was reduced by 67% at the experimental sites compared with that at the control sites, and t he amount of bone loss was reduced by 60%. All results were statistica lly significant (p < 0.01). These findings indicate that a significant component of the pathologic process of periodontitis is due to IL-1/T NF activity, since inhibiting IL-1/TNF reduces both inflammatory cell recruitment and bone loss. The data also suggest that inflammation ass ociated with gingivitis is actively protective, since blocking further up-regulation of the host response with IL-1/TNF inhibitors does not cause periodontal damage. Furthermore, these results coupled with rece nt evidence that IL-1 and TNF participate in endocrine-associated oste oporosis suggest that multiple pathologies involving excessive loss of bone may operate through a common mechanism involving IL-1 and/or TNF .