Gamma Interferon Positively ModulatesActinobacillus actinomycetemcomitans-Specific RANKL⁺CD4⁺Th-Cell-Mediated Alveolar Bone Destruction In Vivo

The Role of Chemokines and Cytokines in the Pathogenesis of Periodontal and Periapical Lesions: Current Concepts

“…Concerning periapical diseases of endodontic origin and periodontitis, IFN- is present at high levels in chronic PLs, and is associated with progressive lesions or higher severity (Colic et al, 2006, Garlet et al, 2003, Honda et al, 2006. In agreement, studies in rodents demonstrated that IFN- is involved in the development of inflammatory reaction and bone resorption in response to A. actinomycetemcomitans and P. gingivalis (Baker et al, 1999, Teng et al, 2005. Interestingly, a controversial role for IFN- in bone lytic lesions have been described, since the association with increased bone loss described in vivo (human and experimental) is not confirmed by in vitro experiments, in which IFN- is described to systematically inhibit osteoclastogenesis , Takayanagi et al, 2005.…”

IFN-γ stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation

“…Moreover, mice lacking IFN-γ production are protected against infection-induced alveolar bone loss (18), and IFN-γ receptor -/-(IFN-γR -/-) mice fail to undergo ovariectomy-induced (ovx-induced) bone loss (2). Furthermore, IFN-γ production correlates positively with tissue destruction in erosive tuberculoid leprosy, and bone resorption in psoriatic arthritis (19,20) increases in parallel with bacterial LPS-induced bone resorption in mice (21) and positively modulates actinobacillus actinomycetemcomitans-specific RANKL + CD4 + Th cell-mediated alveolar bone destruction in vivo (22). Further support for the hypothesis that IFN-γ does not inhibit bone resorption in vivo was provided by the outcome of randomized controlled trials which have shown that IFN-γ does not prevent bone loss in patients with RA (23,24) or the bone-wasting effect of cyclosporin A (16).…”

Interleukin-10 Inhibits Gram-Negative-Microbe-Specific Human Receptor Activator of NF-κB Ligand-Positive CD4 + -Th1-Cell- Associated Alveolar Bone Loss In Vivo

“…ϩ Th cells in vivo and (ii) increased hIFN-␥ coexpression in pathogen-reactive RANKL ϩ Th cells is associated with elevated alveolar bone loss (19,30,32). In this study, to assess the effects of an anti-inflammatory cytokine on RANKL ϩ Th cells coexpressing hIFN-␥ during periodontal pathogenesis, we injected hIL-10 (200 ng/mouse, administered intraperitoneally; 50 to 250 ng tested; BD Pharmingen) (32) or phosphate-buffered saline (sham control) into A. actinomycetemcomitans-infected HuPBL-NOD/SCID mice (five or six mice/human peripheral blood leukocyte [HuPBL] donor/ group) twice a week for the first 3 weeks, as described previ-ously (30,32).…”

“…The study of osteoimmunology has demonstrated that host immune responses, especially T-cell immunity, play a pivotal role in regulating osteoclastogenesis and bone remodeling (26,(32)(33)(34)(35)36). The recently identified tumor necrosis factor (TNF) family molecule receptor activator of NF-B ligand (RANKL), its receptor RANK, and its natural antagonist, osteoprotegerin (OPG), have been shown to be the key regulators of bone remodeling involved in differentiation, activation, and survival of osteoclasts and osteoclast precursors (35).…”