CYTOKINES RELEASED BY GRANULOCYTES ACID MONONUCLEAR-CELLS STIMULATE AMNION CELL PROSTAGLANDIN E(2) PRODUCTION

Preterm labor is associated with histologic chorioamnionitis and intraamniotic infection. Chorioamnionitis is characterized by infiltration of the fetal membranes by granulocytes. In intraamniotic infection, white cells accumulate in amniotic fluid. Granulocytes and mononuclear cells have been shown to release products that stimulate prostaglandin E(2) (PGE(2)) production by amnion cells. The aim of the present study was to identify some of these products. Cell-free supernatant obtained from formylmethionyl-leucyl-phenylalanine (FMLP)-activated granulocytes was subjected to size exclusion chromatography. The fractions obtained were analyzed for their stimulatory effect on PGE(2) production by human amnion cells in culture. Two peaks of PGE(2)-stimulatory activity were found. The activity present in one of these was synergistic with interleukin-1 beta (IL-1 beta) in stimulating amnion cell PGE(2) production and was found to contain mainly transforming growth factor-alpha (TGF-alpha) immunoreactivity. This cytokine originated at least in part from eosinophils. The PGE(2)-stimulatory activity present in the other peak contained IL-1 beta, epidermal growth factor (EGF), and tumor necrosis factor-alpha (TNF-alpha). The release of IL-beta, TNF-alpha, TGF-alpha, and EGF by granulocytes differed from that of mononuclear cells. We have previously shown that TGF-alpha and EGF are synergistic with IL-1 and TNF-alpha in enhancing amnion cell PGE(2) production. The different pattern of prostaglandin-stimulatory cytokines released from different types of white cells suggest that the cells may potentiate each others' effects.