IFN-α and IL-12 induce IL-18 receptor gene expression in human NK and T cells

IL-18 is a proinflammatory cytokine that enhances innate and specific Thl immune responses. During microbial infections, IL-18 is produced by activated macrophages. IL-18 exerts its effects in synergy with IFN-alpha or IL-12 to induce IFN-gamma. Here we show that in human NK and T cells IFN-alpha and IL-12 strongly up-regulate mRNA expression of the IL-18R components, accessory protein-like (AcPL) and IL-1R-related protein (LL-1Rrp), In addition, IFN-alpha enhanced the expression of MyD88, an adaptor molecule involved in IL-18 signaling. Pretreatment of T cells with IFN-alpha or IL-12 enhanced IL-18-induced NF-kappa B activation and sensitized the cells to respond to lower concentrations of IL-18, AcPL and IL-1Rrp genes were strongly expressed in T cells polarized with IL-12, whereas in IL-4-polarized cells these genes were expressed at very low levels, indicating that AcPL and IL-1Rrp genes are preferentially expressed in Thl cells. In conclusion, the results suggest that IFN-alpha and IL-12 enhance innate as well as Thl immune response by inducing IL-18R expression.