Interleukin-1α and tumor necrosis factor α cause placental injury in the rat

Bacterial endotoxins (LPS) causes placental injury and fetal demise in pregnant animals. Because several biological effects of LPS are mediated by interleukin-1 (IL-1) and tumor necrosis factor (TNF), the hypothesis that these cytokines could cause placental injury similar to that seen in LPS-treated pregnant rats was tested. On day 12 of gestation, rats were injected intraperitoneally with saline, LPS, native or heat-inactivated (HI) rHIL1α, or rHTNFα. Seven days later, grossly abnormal implantation sites and fetal demise were observed in rats injected with rHIL-1, rHTNF, or LPS but not in those injected with saline or HI-cytokines. Necrosis of placental, decidual, and fetal tissues was observed in cytokine-treated animals. The necrosis was more severe in LPS-treated rats, in which no fetal remains were identifiable. These data suggest that IL-1 and TNF may play a role in the fetoplacental injury observed in LPS-treated pregnant rats.