Secretion of Interleukin-1β and Interleukin-6 by Fragments of Term Human Placental Villi: Signalling Pathways and Effects of Tumour Necrosis Factor α and Mode of Delivery

The regulation of cytokine secretion has not been extensively investigated in placental tissue. Fragments of term human placenta were incubated in Tyrode's medium for 3h and cytokine concentrations were measured in the supernatant. IL-1β secretion after vaginal delivery (VD) was (mean±sem fmol/mg wet weight/3h) 0.193±0.005 (basal) and 0.549±0.18 (+1n m TNFα) and was more sensitive to TNFα dose after elective Caesarean section in the absence of clinical labour (CS) than VD. Secretion of IL-6 after VD was 2.3±0.47 (basal) and 3.01±0.34 (+1n m TNFα), was correlated with the secretion of IL-1β and was more sensitive to TNFα dose after VD than CS. The inhibitors SB203580, PD98059, SN50, cycloheximide and D-ribofuranosylbenzimidazole each reduced the basal and TNFα-stimulated secretion of IL-1β and also reduced IL-6 secretion with the exception of SN50. There were no interactions between effects of inhibitors and mode of delivery or TNFα. In summary we found that term placenta spontaneously secretes IL-1β and IL-6 in vitro. Delivery after labour alters placental sensitivity to TNFα. Exposure to agents known to inhibit MAPK pathways, NF-κB, or synthesis of protein and mRNA reduces placental cytokine secretion.