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(American Journal of Pathology. 1999;155:2145-2152.)
© 1999 American Society for Investigative Pathology

Regular Articles

Interleukin-1 and Tumor Necrosis Factor Receptor Signaling Is Not Required for Bacteria-Induced Osteoclastogenesis and Bone Loss but Is Essential for Protecting the Host from a Mixed Anaerobic Infection

Chih-Ping Chen^*, Marc Hertzberg^*, Yanling Jiang and Dana T. Graves^*

From the Departments of Periodontology and Oral Biology^*
and Endodontics,
Boston University School of Dental Medicine, Boston University, Boston, Massachusetts

Bacterial infection causes significant morbidity, mediated in part by the up-regulation of inflammatory cytokines. Cytokine induction is thought to stimulate osteolysis in conditions such as periodontal disease and otitis media. To establish the relative importance of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in mediating the response to a mixed anaerobic infection, we used an in vivo model in which the dental pulp was inoculated with six anaerobic pathogens, in mice with functional deletions of receptors to IL-1 (IL-1RI^-/-), TNF (TNFRp55^-/--p75^-/-), or both (TNFRp55^-/--IL-1RI^-/-). Polymorphonuclear and mononuclear phagocyte recruitment occurred to the greatest extent in TNFRp55^-/--IL-1RI^-/- mice, and to a lesser extent in IL-1RI^-/- or TNFRp55^-/--p75^-/- mice, and the least in wild-type mice, demonstrating that recruitment of these phagocytes is not dependent on IL-1 or TNF receptor signaling. A similar pattern was observed for bacterial penetration into host tissue. Because it had recently been reported that TNF played a critical role in mediating lipopolysaccharide-induced bone loss, we anticipated that mice with targeted deletions of TNFRp55^-/- would have reduced osteoclastogenesis. Surprisingly, osteolytic lesion formation was greatest in animals lacking TNF and/or IL-1 receptors. These results indicate that IL-1 or TNF receptor signaling is not required for bacteria-induced osteoclastogenesis and bone loss, but does play a critical role in protecting the host against mixed anaerobic infections.

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