title: IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo.
abstract: 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.
authors.affiliation: Department of Cytokine Biology, The Forsyth Institute, Boston, MA 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: L
authors.initials: L
authors.lastname: Hou
authors.forename: A
authors.initials: A
authors.lastname: Belani
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Uchiyama
authors.forename: R
authors.initials: R
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Stashenko
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D016905:Gram-Negative Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010485:Periapical Periodontitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D016753:Interleukin-10; D015847:Interleukin-4