The role of interleukin‐1α in the pathogenesis of periapical bone destruction in a rat model system

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Abstract
To identify the mediators that stimulate periapical bone resorption following infection, a rat model system was used in which active (rapid) and chronic (slow) phases of bone destruction can be distinguished. Extracts of inflammatory tissues from active lesions contained high levels of bone‐resorbing activity, which was destroyed by proteinase K and heat (70°C), but was unaffected by polymyxin B, indicating the presence of protein mediator(s) rather than lipopolysaccharide. Fast‐performance liquid chromatography gel filtration of extracts of active lesions demonstrated that most activity was associated with macromolecules of MW 30–60 kDa and 15–20 kDa, consistent with bone resorptive cytokines, including interleukin 1 (IL‐I) and tumor necrosis factor (TNF). Inhibition with cytokine‐specific antisera demonstrated that resorbing activity in active lesions was significantly neutralized by anti‐IL‐1β, whereas anti‐IL‐1/α, anti‐TNFα and anti‐TNFα had only slight effect. A lower amount of resorbing activity was present in extracts of chronic lesions, which was also neutralized only by anti‐IL‐1α. Inflammatory tissue explants produced more IL‐1α than 1L‐1βin vitro, confirming findings with extracts, and high levels of IL‐1α were present in active lesions by radioimmunoassay. These data indicate that bone resorption stimulated by bacterial infection is primarily mediated by IL‐1α in this model. The similarity of cytokines in active and chronic lesions suggests that quantitative rather than qualitative differences in these mediators may account for lesion progression.