IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo

Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1 alpha in the murine model. The production and activity of IL-1 alpha is modulated by a network of regulatory cytokines, including those produced hy Th1 (proinflammatory) 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-1 alpha production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4(-/-) exhibited decreased IL-1 alpha production (p < 0.05). IL-10 also suppressed IL-1 alpha 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-1 alpha expression.