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Intrauterine infection is an important cause of preterm labor and delivery and is characterized by increased production of inflammatory cytokines by gestational tissues. We evaluated the biosynthesis of the inflammatory cytokine interleukin-6 (IL-6) by human chorion laeve cells and its regulation by other cytokines essential to the inflammatory process. We found that cultured chorion cells secrete IL-6 in the presence of growth medium supplemented only with 10% fetal calf serum. IL-1 beta, tumor necrosis factor, and lipopolysaccharide all induced a significant concentration-dependent stimulation of IL-6 production by chorion cells. The concentration range of each cytokine tested (0.1-10 ng/mL) is within the range of values found in the amniotic fluid of women destined to deliver preterm due to infection of gestational tissues. Additionally, treatment of chorion cells with IL-1 beta in combination with actinomycin-D or cycloheximide attenuated the stimulatory action of IL-1 beta on IL-6 production. Northern blot analysis of total RNA from cultured chorion cells stimulated with IL-1 beta demonstrated that IL-6 mRNA increases over time. Our data suggest that IL-6 is produced by human fetal chorion in response to infection of maternal gestational tissues. In conjunction with other inflammatory mediators, fetally derived IL-6 may play a role in the pathophysiology of preterm labor due to infection.

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Changes in oxytocin (OT) receptor expression have been found to be an important determinant of the physiological effect of OT in several species. To date there are no published studies of OT binding sites during pregnancy in the pig. The purpose of the present study is to improve understanding of the role of OT in porcine parturition. The concentration and affinity of OT binding sites were determined for myometrium and endometrium from pregnant and postpartum gilts. Tissues were obtained after slaughter from 7 animals in each of four groups: 1) 90 days gestation, 2) 112 days gestation, 3) term after milk letdown (before delivery), and 4) within 1-3 h after farrowing. Mammary tissues were obtained for some animals in each group (n = 3-5/group). Before slaughter, blood was collected from each animal and assayed for estradiol-17 beta, progesterone, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), and OT. Binding of 3H-OT in the three tissues was concentration- and time-dependent. Sites of 3H-OT binding (fmol/mg protein +/- SEM) increased toward term for each tissue and remained elevated in the postpartum group. Endometrial and mammary tissues displayed the most acute increases in OT binding site concentrations while myometrial tissues displayed a more gradual increase in OT binding sites over the times studied. The binding sites displayed high affinity for 3H-OT and were characterized by linear Scatchard plots. Concentrations of estradiol-17 beta, PGFM, and OT (pg/ml +/- SEM) were positively correlated with 3H-OT binding site concentrations, whereas progestrone concentrations (ng/ml +/- SEM) were negatively correlated with binding site concentration, as determined by Pearson's Correlation Analysis. The data represent the first account of changes in the expression of OT binding sites on porcine tissues during gestation and labor.