Interleukin-1 alpha and tumor necrosis factor alpha 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) rHIL 1 alpha, or rH-TNF alpha. 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.