Human fetal membrane expression of IL-19 and IL-20 and its differential effect on inflammatory cytokine production

Objective. The objectives of this study were to document the expression of IL-19 and IL-20, localize their expression in human fetal membranes and to examine their influence on the production of other inflammatory cytokines (IL-1, IL-6, IL-8, and TNF-alpha) from placental membranes. Methods. Human fetal membranes collected at term from normal pregnancies were stimulated with either recombinant human IL-19, IL-20, bacterial endotoxin (LPS) alone or the cytokine + LPS. The expression of IL-19 and IL-20 was studied by reverse transcriptase polymerase chain reaction (RT-PCR) and localized using immunohistochemistry. Concentrations of IL-1, IL-6, IL-8, and TNF-alpha were measured with multiplex sandwich immunoassay using microsphere technology. Results. RT- PCR documented IL-19 and IL-20 gene expression in fetal membranes. Immunohistochemistry localized both peptides to amnion and chorion layers. LPS stimulated the production of all four cytokines (IL-1, IL-6, IL-8, and TNF-alpha) from fetal membranes compared to unstimulated controls. No change in IL-1 and IL-8 concentration was seen after IL-19 or IL-20 stimulation, whereas IL-6 concentration was three-and two-fold higher after IL-19 and IL-20 treatment, respectively. TNF levels were unchanged after IL-19 and IL-20 treatment; however, TNF levels were significantly decreased in membranes treated with IL-19 or IL-20+LPS compared to LPS alone. Conclusion. Fetal membranes are a source of IL-19 and IL-20. These cytokines act as an inhibitory agent to LPS-induced TNF production whereas they stimulate IL-6 production and have no effect on IL-1 and IL-8 production from human fetal membranes. The effect of IL-19 and IL-20 in pregnancy will be dependent on their concentrations and other environmental factors such as infection.