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-1α in the murine model. The production and activity of IL-1α 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-1α production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4−/− exhibited decreased IL-1α production (p < 0.05). IL-10 also suppressed IL-1α 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-1α expression.

T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice

“…As shown in Fig. 3, P. gingivalis stimulation induced a significant elevation in IL-1␣ in Stat3-deficient MP (Ͼ10-fold), supporting our previous finding (27). In addition, Stat3-deficient MP also exhibited a vigorous up-regulation of both IL-12p70 (not detectable in wild-type MP) and IL-10 (8-fold) production compared with wild-type MP following P. gingivalis stimulation.…”

“…Resident peritoneal MPs from MP/PMN-specific Stat3-deficient and wildtype mice were isolated and cultured in RPMI 1640 (Sigma-Aldrich) supplemented with 10% FBS (Sigma-Aldrich) and 2 mM L-glutamine (Invitrogen) (27). Isolated MPs, plated at 10 5 cells/well in 96-well plates (n ϭ 4), were stimulated with fixed P. gingivalis W83 for 24 h at 37°C in an atmosphere of 5% CO 2 /95% air.…”

Differentiation of entamoeba histolytica/entamoeba dispar by PCR and their correlation with humoral and cellular immunity in individuals with clinical variants of amoebiasis.

“…Protective immunity would be associated with Th1 cells that produce INF-␥ and IL-2, whereas Th2 cells, which produce immunosuppressive IL-4 and IL-10, could facilitate the survival and dissemination of the parasite generating tissue damage and the appearance of the disease. Recent evidence [61][62][63] suggests an important role for IL-10, but not for IL-4 in the Th2 response. However, as has been proposed by others, [64][65][66][67] we analyzed IL-4 and IFN-␥ as indicators of Th2 and Th1, respectively.…”

Th1 Immune Response Promotes Severe Bone Resorption Caused by Porphyromonas gingivalis

“…7 Interleukin (IL)-1 has been strongly associated with alveolar bone resorption via stimulation of receptor activator of nuclear factor B ligand (RANKL) expressed by osteoblasts and lymphocytes, 8 -12 although other mediators, particularly those derived from T cells, may also play critical roles by modulating inflammation. 8,[13][14][15][16][17] Both Th1 and Th2 cytokines are expressed after dental pulp infection, with Th1 expression becoming predominant after several weeks. 18 Paradoxically, gene knockouts of the prototype Th1 mediator interferon (IFN)-␥ or IFN-␥-inducing cytokines IL-12 and IL-18 have no significant effect on periapical bone destruction, 19 suggesting either a lack of regulatory activity or functional redundancy in pro-inflammatory pathways.…”