Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation

Periapical bone destruction earlier was shown to be mediated primarily by interleukin (IL)-1α in a rat model. The production and action of IL-1α is in turn potentially modulated by a network of cytokines, which are produced by infiltrating T-helper type 1 (Th1) and type 2 (Th2) lymphocytes, and resident connective tissue cells within the lesion. This study was designed to examine the kinetics of expression of 10 cytokines in experimentally induced murine periapical lesions, including bone-resorptive [IL-1α, tumour necrosis factor α (TNFα), IL-6, IL-11], Th1-type [IL-2, IL-12, interferon-γ (IFNγ)] and Th2-type (IL-4, IL-6, IL-10, IL-13) mediators. Cytokine mRNA expression was assessed qualitatively by reverse transcription-polymerase chain reaction, and cytokine proteins quantified by enzyme-linked immunosorbent assay. IL-1α and TNFα protein and mRNA were highly expressed, beginning on day 7, and increased to day 28. IL-6 increased to day 14 and then declined, whereas the expression of IL-11 was not modulated by pulp exposure. Most of the Th1-type cytokines, including IL-2, IL-12, and IFNγ, showed an increase in mRNA and/or protein expression in periapical lesions after pulpal exposure; the expression of Th2-type cytokines was similarly increased, but had declined at the latest time-point (day 28), suggesting possible inhibition by Th1-type mediators. Significant correlations were observed between levels of IL-1α and Th1-derived pro-inflammatory mediators IL-2, IL-12, TNFα, and IFNγ. There was a lack of correlation between IL-1α and Th2-type anti-inflammatory mediators, including IL-4, -6, and -10. These results indicate that a cytokine network is activated in the periapex in response to bacterial infection, and that Th1-modulated pro-inflammatory pathways may predominate during periapical bone destruction.