IL-1β is a better inducer of apoptosis in human fetal membranes than IL-6

The objective of this study was to compare two of the inflammatory cytokines (IL-1 and IL-6) elevated in both preterm labour and preterm premature rupture of the membranes (pPROM), with respect to their ability to induce fetal membrane apoptosis. Fetal membranes collected from women at term were placed in an organ explant system and stimulated with recombinant human IL-1beta and IL-6. The expression patterns of pro-apoptotic genes (Fas, FasL, TRADD, FADD) and caspases 2, 3, 8, 9 were studied using PCR. Caspase activity and DNA fragmentation were studied using substrate assays and TUNEL respectively. Caspase 8 and 9 expressions were induced in IL-1beta and IL-6 treated amniochorion. Caspase 2 expression was seen only in IL-1beta stimulated tissues. When compared to control, IL-1beta increased caspase 2, 3, 8 and 9 activities, whereas IL-6 treated membranes did not exhibit a significant change. DNA fragmentation was seen in greater numbers after IL-1beta treatment than after IL-6 treatment. This study demonstrates that IL-1beta is a better inducer of apoptosis in normal human fetal membranes than IL-6. (C) 2003 Elsevier Ltd. All rights reserved.