Abstract
IL-18 has pro- and anti-inflammatory effects. However, only a few studies have demonstrated its role in reproduction. Here, we developed the fetal growth restriction model mouse and examined the effect of IL-18 on fetal growth. The C57BL/6 female mice were mated with the BALB/c male mice, the anti-IL-18 neutralizing antibody was administered intraperitoneally, and the placenta and birth weight were measured. The pregnant uteri were analyzed using flow cytometry, western blotting, and immunofluorescence staining. The blockade of IL-18 significantly decreased in placenta and birth weight compared with control. The blockade of IL-18 also induced a decreased production of IFN-γ in the uterine T cells and NK cells, M2-polarization of uterine macrophages, and suppressed IL-12 production. Histologically, the vascular remodeling failure of the placental labyrinth was shown in mice with the blockade of IL-18. Importantly, we found that macrophages and smooth muscle cells are essential sources of IL-18. These findings indicate that IL-18 enhances an appropriate type 1 immune response leading to the proper placental development and fetal growth via the feedback between IFN-γ and IL-12.
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