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Clinical and Diagnostic Laboratory Immunology, January 2004, p. 106-110, Vol. 11, No. 1
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.1.106-110.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Gamma Interferon (IFN-) and IFN--Inducing Cytokines Interleukin-12 (IL-12) and IL-18 Do Not Augment Infection-Stimulated Bone Resorption In Vivo

Department of Cytokine Biology,¹ Department of Immunology, The Forsyth Institute, Boston, Massachusetts,⁴ Division of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia,² Pulp Biology and Endodontics, Department of Restorative Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo,³ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan⁵

Received 22 August 2003/ Returned for modification 15 October 2003/ Accepted 29 October 2003

Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-) and IFN--inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12^-/-, IL-18^-/-, and IFN-^-/- mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12^-/-, IL-18^-/-, and IFN-^-/- mice had similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-^-/- mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1 levels. Recombinant IL-12, IL-18, and IFN- individually failed to consistently modulate macrophage IL-1 production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN- do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways.