interleukin-8 and Fetal-Hypoxia

The source and clearance of cytokines in the fetal circulation in term pregnancies complicated by chorioamnionitis remains unclear as are the contributions of placental transport, synthesis, and clearance. The objectives of the study were to determine (1) fetal and/or placental contributions to synthesis and/or clearance of inflammatory and anti-inflammatory cytokines in term pregnancies complicated by chorioamnionitis and (2) whether this differs in pregnancies further complicated by fetal hypoxia.. Prospective cohort study of pregnancies >37 weeks gestational age that included: Group 1, uncomplicated cesarean delivery without labor (n = 20); Group 2, uncomplicated vaginal delivery (n = 30); Group 3, pregnancies complicated by chorioamnionitis (n = 10); Group 4, complicated by chorioamnionitis + fetal hypoxia (n = 10). Umbilical arterial (UmA) and venous (UmV) blood were assayed for IL-1β, IL-2, IL-6, IL-8, TNFα, and IL-10.. IL-6 and IL-8 were below assay detection in UmA and UmV blood in Group 1 and increased in Group 2 (P < 0.01), UmA»UmV (P < 0.01). Their concentrations increased further in Groups 3 and 4 (P = 0.003), UmA»UmV. Placental clearance was concentration dependent that approaches saturation in the presence of chorioamnionitis.. Marked increases in fetal synthesis of IL-6 and IL-8 occur in chorioamnionitis. Synthesis increase further when complicated by fetal hypoxia. Cytokine removal occurs via placental concentration-dependent mechanisms, potentially contributing to adverse fetal effects.. The source and role of the placenta in synthesis and/or clearance of inflammatory mediators in term pregnancies complicated by clinical chorioamnionitis are unclear; however, conventional wisdom suggests the placenta is their source. This is the first study demonstrating that circulating concentrations of fetal IL-6 and IL-8 in clinical chorioamnionitis ± birth asphyxia in term pregnancies are of fetal origin. Circulating fetal inflammatory cytokines are cleared by concentration-dependent placental mechanisms that are nearly saturated in chorioamnionitis ± fetal hypoxia. These observations provide additional insight into understanding the fetal immune response in term pregnancies complicated by clinical chorioamnionitis.

Topics: Chorioamnionitis; Cytokines; Female; Fetal Hypoxia; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Placenta; Pregnancy; Prospective Studies

We hypothesized that repetitive umbilical cord occlusions (UCOs) with worsening acidosis will lead to a fetal inflammatory response.. Chronically instrumented fetal sheep underwent a series of UCOs until fetal arterial pH decreased to <7.00. Maternal and fetal blood samples were taken for blood gases/pH and plasma interleukin (IL)-1B and IL-6 levels. Animals were euthanized at 24 hours of recovery with brain tissue processed for subsequent measurement of microglia and mast cell counts.. Repetitive UCOs resulted in a severe degree of fetal acidemia. Fetal plasma IL-1B values were increased approximately 2-fold when measured at maximal fetal acidosis and again at 1-2 hours of recovery. Fetal microglia cells were increased approximately 2-fold in the white matter and hippocampus, while mast cells were increased approximately 2-fold in the choroid plexus and now evident in the thalamus when analyzed at 24 hours recovery.. Repetitive UCOs leading to severe acidemia in the ovine fetus near term will result in an inflammatory response both systemically and locally within the brain.

Topics: Acidosis; Animals; Cerebrovascular Circulation; Constriction, Pathologic; Enzyme-Linked Immunosorbent Assay; Fetal Diseases; Fetal Hypoxia; Fetus; Hippocampus; Immunohistochemistry; Interleukin-6; Interleukin-8; Mast Cells; Microglia; Sheep; Umbilical Cord

Placental hypoxia and altered placental cytokine productions have been considered to play a significant role in the pathophysiology of preeclampsia. The objective of this study was to determine whether hypoxia could modify interleukin (IL)-6, IL-8, and IL-10 production by placental trophoblast cells (TCs) from normal and preeclamptic (PE) pregnancies.. Placentas were obtained from nine normal and nine PE pregnancies immediately after delivery. Placental TCs were isolated and cultured under normoxic (21% O(2)/air) and hypoxic (2% O(2)/5% CO(2)/92% N(2)) conditions for 48 hours. TC productions of IL-6, IL-8, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). Unpaired t tests or paired t test was used for the statistical analysis and data are expressed as means +/- SE (pg/mug cellular protein). A P value less than .05 was considered statistically significant.. PE-TCs produced significantly more IL-6, IL-8, and IL-10 than those of normal-TCs when they were cultured under normoxic condition, P < .05. Both normal-TCs and PE-TCs produced more IL-6 and IL-8 when they were cultured under hypoxic conditions. Hypoxia reduced IL-10 production by PE-TCs, but had no effect on IL-10 production by normal-TCs.. Hypoxia promotes both IL-6 and IL-8 but reduces IL-10 production by placental TCs from PE pregnancies.

Topics: Adult; Down-Regulation; Female; Fetal Hypoxia; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Placenta; Pre-Eclampsia; Pregnancy; Trophoblasts; Up-Regulation

Our purpose was to investigate the participation of cytokines and neutrophils in fetal distress.. Umbilical cord serum interleukin-6 (IL-6), interleukin-8 (IL-8), and plasma granulocyte elastase (GEL) were measured in 30 normally grown newborns without fetal distress (Group A), 10 growth-retarded newborns without acute fetal distress (Group B), 5 normally grown newborns with fetal distress (Group C), and 5 growth-retarded newborns with fetal distress (Group D). Umbilical arterial blood pH and PO2 were also measured.. Umbilical arterial blood pH and PO2 in either Group C or Group D were significantly lower than those in either Group A or Group B. The concentration of IL-6 in Group D was significantly higher than that in either Group A, B, or C. The level of IL-8 in either Group C or Group D was significantly higher than that in either Group A or Group B. The concentrations of GEL in Group D was significantly higher than that in either Group A or Group B.. This study suggests that fetal distress in utero causes an elevation of immune factors such as IL-6, IL-8 and GEL.

Topics: Acidosis; Fetal Blood; Fetal Distress; Fetal Growth Retardation; Fetal Hypoxia; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Leukocyte Elastase