Effects of IFN-γ on IL-18 Expression in Pregnant Rats and Pregnancy Outcomes

The present study focused on establishing the effects of interferon-gamma (IFN-gamma) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-gamma (L-IFN-gamma) and high IFN-gamma groups (H-IFN-gamma) that received normal saline, 100 IU/g of IFN-gamma and 500 IU/g of IFN-gamma vaginal muscular injection, respectively. The effects of IFN-gamma on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. LL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-gamma group compared to the L-IFN-gamma and control groups (p<0.01), indicating that high doses of IFN-gamma induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-gamma group was lower than that of the L-LFN-gamma group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-gamma group was significantly higher than those in the control and L-IFN-gamma groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-gamma and control groups. However, for the H-IFN-gamma group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-gamma plays a regulatory role in M-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-gamma influence normal pregnancy at the early stages in rats by downregulating M-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.