PROBLEM:
    IL-18 is a novel cytokine, which promotes inflammation and apoptosis. This study examines its expression pattern, site of production and levels in the amniotic fluid (AF) during pregnancy complications like preterm labor, preterm premature rupture of membranes (pPROM). The ability of IL-18 to induce the Fas-FasL/caspase mediated apoptotic pathway was also studied.

METHODS:
    Amniochorion collected at term was placed in an organ explant system. IL-18 mRNA expression was studied by RT-PCR. IL-18 mRNA and peptide were localized by in situ hybridization and immunohistochemistry. IL-18 in the amniotic fluid (AF) of women with pPROM, preterm labor with no rupture of membranes, and at term was measured using ELISA. Multiple PCR was used to study the expression pattern of pro-apoptotic genes like Fas, Fas ligand (FasL), caspase 8 and Fas associated death domain (FADD). ELISA was also used to measure the release of soluble Fas from IL-18 stimulated amniochorion in culture media.

RESULTS:
    IL-18 is a constitutively expressed gene in human chorion and decidua but not in amnion and increases in the AF of women with pPROM (2.9 ng/ml; SD +/- 3.3) compared to women with preterm labor (1.1 ng/ml; SD+/- 0.67; p < 0.05) and term (0.9 ng/ml; SD+/- 0.73; p < 0.05). IL-18 induces Fas expression whereas FADD is a constitutively expressed gene in human fetal membranes. IL-18 failed to induce FasL or caspase 8 expressions. Soluble Fas release from amniochorion was increased after IL-18 stimulation.

CONCLUSION:
     Chorion and decidua are a source of IL-18, whose concentrations are increased in AF during pPROM. IL-18 induced Fas expression in amniochorion; however, it failed to turn on other genes of the Fas-FasL apoptosis pathway including FasL and caspase 8.