IL-10, But Not IL-4, Suppresses Infection-Stimulated Bone Resorption In Vivo

• Published in: The Journal of immunology (1950) Vol. 165; no. 7; pp. 3626 - 3630
• Main Authors: Sasaki, Hajime, Hou, Linda, Belani, Anita, Wang, Cun-Yu, Uchiyama, Toru, Muller, Ralph, Stashenko, Philip
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.2000
• Subjects: Animals; Bone Resorption - genetics; Bone Resorption - immunology; Bone Resorption - microbiology; Bone Resorption - pathology; Cells, Cultured; Cytokines - biosynthesis; Disease Models, Animal; Gram-Negative Bacterial Infections - genetics; Gram-Negative Bacterial Infections - immunology; Gram-Negative Bacterial Infections - pathology; Gram-Positive Bacterial Infections - genetics; Gram-Positive Bacterial Infections - immunology; Gram-Positive Bacterial Infections - pathology; Immunosuppressive Agents - administration & dosage; Interleukin 1^a; Interleukin-1 - biosynthesis; Interleukin-10 - administration & dosage; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - physiology; Interleukin-4 - administration & dosage; Interleukin-4 - deficiency; Interleukin-4 - genetics; Interleukin-4 - physiology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - microbiology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Periapical Periodontitis - genetics; Periapical Periodontitis - immunology; Periapical Periodontitis - microbiology; Periapical Periodontitis - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.7.3626

Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1alpha in the murine model. The production and activity of IL-1alpha is modulated by a network of regulatory cytokines, including those produced by Th1 (pro-inflammatory) and Th2 (anti-inflammatory) subset T cells. This study was designed to assess the functional role of the Th2-type cytokines IL-4 and IL-10 in infection-stimulated bone resorption in vivo. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21. The results demonstrate that IL-10(-/-) mice had significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice (p < 0.001), whereas IL-4(-/-) exhibited no increased resorption. IL-10(-/-) had markedly elevated IL-1alpha production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4(-/-) exhibited decreased IL-1alpha production (p < 0.05). IL-10 also suppressed IL-1alpha production by macrophages in a dose-dependent fashion in vitro, whereas IL-4 had weak and variable effects. We conclude that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1alpha expression.