Murine fetal resorption and experimental pre-eclampsia are induced by both excessive Th1 and Th2 activation

Cytokines: Important for implantation?

“…In humans, abnormal regulation correlates with a pathologic subendometrial vascular flow index (VFI), and IL-15 levels correlate with high IL-18 levels in sterile patients, but not completely with excess NK counts so that the main effects are likely NK cytotoxic activation rather than replication which seems more strongly correlated to the ratio IL-18/IL-18 BP [33,34]. Experimentally, as stated above injection of high doses of IL-12 or IL-18, or both, produce abortion and /or a pre eclampsia like syndrome in mice [130,171,172].…”

“…NK-lineage cells infiltrating the uterus were activated as early as day 6.5 to massively secrete IL-18 (a cytokine that promotes secretion of IFN-γ), and there was more IL-18, in the non abortion prone mating with BALB/c than in the abortion prone one with DBA/2 [129]. Yet, IL-18, alone, or with IL-12, is abortifacient in established pregnancy, and has been implied to play a role in a murine preeclampsia model, as first reported by a Japanese group [130]. The role of uterine NK (uNK) cells was further elucidated by Guimond et al [25,128,131]: NK deficient TgE26 mice (which also have a T cell defect) had profound reproductive defect with reduced placental size and lack of transformation of the uterine arteries which retained too thick arterial walls, a feature ultimately leading to a high percentage of fetal deaths.…”

Introducing a mouse model for pre‐eclampsia: adoptive transfer of activated Th1 cells leads to pre‐eclampsia‐like symptoms exclusively in pregnant mice

“…Over the past decade, various mammalian models to investigate the pathophysiology of PE have been suggested; however, their validity was hampered by the fact that in most of them, the non-pregnant control animals also developed PE-like symptoms [14][15][16][17][18][19]. Here, we introduce a new model in which activated Th1 cells are transferred into pregnant or non-pregnant recipients, which leads to PE-like symptoms exclusively in pregnant mice.…”

“…To date, some PE animal models have been proposed in the rabbit, rat and mouse [14][15][16][17][18][19]. The experimental design of such models was primarily based on mechanisms involved in the regulation of vasoconstriction/ vasodilation, i.e.…”

“…Other, rather immunologically based models, included the administration of low doses of endotoxin, which led to PE-like symptoms exclusively in pregnant rats [6]. Further, the transfer of lymphocytes that had been incubated in IL-4 and IL-12 into pregnant mice, but not of lymphocytes that had been polyclonally or monoclonally activated, has been described [18]; this led to an increase in blood pressure in pregnant mice compared with pregnant animals given mock-treated cells. However, data delineating the pregnancy-specificity of these symptoms were not provided.…”