Oxytocin signaling in human myometrium is impaired by prolonged exposure to interleukin-1

Intra-amniotic infection leads to preterm labor and is associated with the local release of inflammatory cytokines by fetal membranes, resulting in th e production of uterotonic prostaglandins, Oxytocin, however, also plays a key role in the initiation of labor, Short-term exposure of myometrium to i nterleukin (IL)-1 enhances oxytocin signaling and contractility, With intra uterine infection, however, myometrium is exposed to inflammatory cytokines for prolonged periods. The present study was conducted to demonstrate that myometrial oxytocin signaling is significantly impaired following prolonge d exposure to IL-1, Myometrial cells were treated with IL-1 for 24 h. Oxyto cin-stimulated inositol trisphosphate (IP3) production was measured in trit iated myoinositol-loaded myometrial cells. Arachidonic acid (AA) release wa s measured in tritiated AA-loaded myometrial cells. Increases in intracellu lar calcium were measure with fluo-3. Prostaglandin (PC) F-2 alpha and 6-ke to-PGF(1 alpha) were measured by ELISA assay, Prolonged exposure of myometr ial cells to IL-1 resulted in a significant reduction in oxytocin-mediated signaling as measured by IP3 production and AA release, as well as a decrea se in intracellular calcium. Prolonged exposure of myometrial cells to IL-1 , however, resulted in enhanced PC release. Oxytocin may not contribute sig nificantly to the labor-inducing action of IL-1 in the setting of preterm l abor with prolonged infection.