A Controversial Role for IL-12 in Immune Response and Bone Resorption at Apical Periodontal Sites

Figure 1

Schematic drawing showing the controversial role of IL-12 on bone resorption at apical periodontal sites. The progression of dental pulp infection triggers an inflammatory response in periapical tissues. Inflammatory cells, such as macrophages, are recruited for that region and release proinflammatory mediators. One of those mediators is IL-12, which induces Th1 cells to produce IFN-γ. The IL-12-IFN-γ pathway can induce bone resorption by production of proinflammatory cytokines, such as TNF-α and IL-1β, which leads to the activation of osteoclasts. In contrast, this pathway is also involved in the degradation of the RANK adapter protein, TRAF6, which reduces RANKL-induced osteoclast differentiation. In this context, dendritic cells and naïve CD4⁺ cells also produce the IL-12 family member cytokine IL-23, which induces the differentiation of Th17 cells. These cells release IL-17, enhancing the IFN-γ production. In favor of this proinflammatory environment IL-12 also may blockade Th2 cytokines, stimulating the progression of infection-induced periapical lesions. These opposing mechanisms may explain the discrepant findings regarding IL-12 and IFN-γ in the pathogenesis of periapical lesions. IFN-γ: interferon-γ; RANK: receptor activator of nuclear factor κB; TRAF6: tumor necrosis factor receptor-associated factor 6.