Role of decidual natural killer cells, interleukin-15, and interferon-γ in placental development and preeclampsia.

Preeclampsia is a hypertensive, proteinuric disease that affects 5-10% of all pregnancies and is a leading cause of maternal and perinatal morbidity/mortality (Soto et al., J Matern Fetal Neonatal Med 25: 498-507, 2011). The primary treatment for preeclampsia still is delivery of the fetus and placenta. The underlying mechanisms remain elusive. One possibility is inadequate uterine angiogenesis/vascularity (decidualization) at the time of implantation (Torry et al., Am J Reprod Immunol 51: 257-268, 2004). Here, we review evidence for dysregulation of decidual natural killer (dNK) cells, which secrete important angiogenic factors during decidualization, as a contributing factor in preeclampsia.

Clinical Problem Solving: A 56-Year-Old Woman With Right Facial Weakness, Numbness, and Diplopia.

We discuss a case of a middle-aged woman with a history of urothelial carcinoma, who presented with subacute progression of double vision, right facial numbness, and back pain. Her MRI brain and spine demonstrated multifocal enhancing lesions at the skull base and throughout the spine. Since her initial serum and cerebrospinal fluid (CSF) studies were unrevealing, she underwent a biopsy of her skull base lesion, which was initially concerning for infection. However, her symptoms worsened despite appropriate antibiotic therapy, necessitating a spinal root biopsy that was consistent with leptomeningeal urothelial carcinoma. Her case illustrates the challenge of accurately diagnosing isolated leptomeningeal metastatic disease, which can be difficult to diagnose from CSF analysis and often requires multiple lumbar punctures to improve sensitivity. While genitourinary cancers rarely metastasize to the CNS, clinicians should retain high suspicion for neoplastic etiologies of leptomeningeal disease in patients with a history of cancer and new neurologic deficits.

Decidual Cox2 inhibition improves fetal and maternal outcomes in a preeclampsia-like mouse model.

Preeclampsia (PE) is a disorder of pregnancy that manifests as late gestational maternal hypertension and proteinuria and can be life-threatening to both the mother and baby. It is believed that abnormal placentation is responsible for the cascade of events leading to the maternal syndrome. Embryo implantation is critical to establishing a healthy pregnancy. Defective implantation can cause adverse "ripple effects," leading to abnormal decidualization and placentation, retarded fetal development, and poor pregnancy outcomes, such as PE and fetal growth restriction. The precise mechanism(s) of implantation defects that lead to PE remain elusive. BPH/5 mice, which spontaneously develop the cardinal features of PE, show peri-implantation defects including upregulation of Cox2 and IL-15 at the maternal-fetal interface. This was associated with decreased decidual natural killer (dNK) cells, which have important roles in establishing placental perfusion. Interestingly, a single administration of a Cox2 inhibitor (celecoxib) during decidualization restrained Cox2 and IL-15 expression, restored dNK cell numbers, improved fetal growth, and attenuated late gestational hypertension in BPH/5 female mice. This study provides evidence that decidual overexpression of Cox2 and IL-15 may trigger the adverse pregnancy outcomes reflected in the preeclamptic syndrome, underscoring the idea that Cox2 inhibitor treatment is an effective strategy for the prevention of PE-associated fetal and maternal morbidity and mortality.