epidermal-growth-factor and Chorioamnionitis

To evaluate the role of interleukins (IL-1, IL-6), tumor necrosis factor alpha (TNFalpha) and for the first time interferon gamma (IFNgamma) and epidermal growth factor (EGF) in the pathogenesis of premature rupture of membranes (PROM) with and without confirmed intrauterine infection.. Amniotic fluid was retrieved by transabdominal amniocentesis from 30 patients with PROM and 20 normal pregnant women with intact membranes of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma whether or not clinical signs of chorioamnionitis were present. Maternal serum and amniotic fluid IL-1, IL-6, TNFalpha and IFNgamma concentrations were determined by the corresponding immunoradiometric assay, whereas EGF concentration was determined by a specific radioimmunoassay.. Nearly all cases of PROM with infection revealed elevated amniotic fluid cytokines (IL-1beta, IL-6, TNFalpha, IFNgamma, EGF) whereas half of them revealed elevated serum cytokines. In cases of PROM without confirmed infection, there were no significant changes of maternal serum cytokines, whereas two-thirds of them revealed elevated amniotic fluid cytokines.. The rise of cytokines in amniotic fluid of cases of PROM with infection may represent: (a) enhanced macrophage activity for immunosurveillance of the fetus; (b) a preparatory step for the initiation of labor; and (c) a valuable tests for diagnosing chorioamnioitis. The mechanism responsible for PROM in the presence or absence of infection is likely to be of different nature.

Topics: Adult; Amniotic Fluid; Chorioamnionitis; Cytokines; Epidermal Growth Factor; Female; Fetal Membranes, Premature Rupture; Humans; Interferon-gamma; Interleukin-1; Interleukin-6; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha

Cell-free supernatant from formylmethionyl-leucyl-phenylalanine (fMLP)-activated granulocytes causes a time- and concentration-dependent stimulation of prostaglandin E2 (PGE2) production in amnion cells. PGE2 concentration in the culture medium after 36 h treatment with granulocyte supernatant (from 40 x 10(6) granulocytes/ml of amnion cell medium), 1.49 +/- 0.71 pg/ng DNA (n = 13), was significantly higher (p = 0.0015) than in control cells (0.33 +/- 0.23 pg/ng DNA, n = 13). Indomethacin abolished this stimulation. Granulocyte supernatant and human epidermal growth factor (hEGF) had an additive effect on amnion cell PGE2 production. Catalase, superoxide dismutase (SOD), protease inhibitors or the platelet-activating factor (PAF) antagonist L-659,989 had no effect. Actinomycin D, cycloheximide and mepacrine reduced the PGE2 production. The phospholipase A2 activity present in granulocyte supernatants was resistant to heating, whereas heating decreased their PGE2-stimulating activity by 92%. Exogenous phospholipase A2 had no effect on PGE2 synthesis. The granulocyte product could be precipitated with ammonium sulphate. On gel filtration of supernatant, two peaks of PGE2-synthesis stimulating activity were obtained (molecular weights 12,000 and 60,000). This data serve to explain the association of chorioamnionitis with preterm labor: activated granulocytes release a protein(s) that induces prostaglandin production in amnion cells, and thus promote labor.

Topics: Amnion; Cells, Cultured; Chorioamnionitis; Cytochalasin B; Dinoprostone; Epidermal Growth Factor; Female; Free Radical Scavengers; Granulocytes; Hot Temperature; Humans; Indomethacin; Labor, Obstetric; N-Formylmethionine Leucyl-Phenylalanine; Obstetric Labor, Premature; Phospholipases A; Phospholipases A2; Platelet Activating Factor; Pregnancy; Protein Synthesis Inhibitors; Stimulation, Chemical