The regulation of interleukin-6 secretion by prostanoids and members of the tumor necrosis factor superfamily in fresh villous fragments of term human placenta.

Abstract

To determine whether prostanoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and members of the tumor necrosis factor superfamily can regulate placental secretion of interleukin-6 (IL-6) and whether labor influences any such effects. Villous fragments of term, human placenta were kept in culture for up to 4 hours, and IL-6 concentrations were measured in the supernatant. We assessed the effects of the following prostanoids: PGE(2), PGF(2alpha), thromboxane A(2) mimetic (U-46619), and carbacyclin, a stable prostacyclin analogue (all at 1 microM); NSAIDs: indomethacin (150 microM) or nimesulide (100 microM); and Fas ligand (5 ng/mL). Secretion (mean +/- standard error) of IL-6 was, for control conditions, 1.92 +/- 0.28 fmol/mg wet weight per 3 hours; for PGE(2), 3.57 +/- 0.29 fmol/mg wet weight per 3 hours, P <.01; and for carbacyclin, 3.11 +/- 0.44 fmol/mg wet weight per 3 hours, P <.01. Incubation with PGF(2alpha) or the thromboxane A(2) analogue, U46619, had no effect on IL-6 secretion under these conditions. Fas ligand stimulated IL-6 secretion (3.06 +/- 0.38 fmol/mg wet weight per 3 hours, P <.05). Labor did not alter the effects of prostanoids or FasL. The effects of NSAIDs were assessed over 4 hours. Secretion (median, interquartile range) was, under control conditions 3.26, 2.83-6.23 fmol/mg wet weight per 4 hours, with indomethacin 1.4, 1.28-3.21 (P <.05), and with nimesulide 0.75, 0.50-1.56 fmol/mg wet weight per 4 hours. The magnitude of the effect of Fas ligand in the presence of NSAIDs depended on whether the placentas were delivered before or after labor. Prostanoids, NSAIDs, and the Fas ligand regulate placental IL-6 secretion. Although the effects of individual agents did not vary with the presence or absence of labor, modulation of IL-6 secretion by labor became apparent when agents were combined.