Prostanoid stimulation of cytokine production in an amnion-derived cell line: Evidence of a feed-forward mechanism with implications for term and preterm labor

OBJECTIVE: To test the hypothesis that amnion cytokine production might be regulated by prostanoids. METHODS: Amnion-derived WISH cells were treated with a range of prostanoids and their effects on production of interleukin (IL)-6 and IL-8 were determ ined by enzyme-linked immunosorbent assay and Northern analysis. The effect s of thromboxane inhibitors on cytokine production by term primary amnion e xplants also were examined. RESULTS: Prostaglandin (PG)A(2), PGD(2), PGF(2 alpha), PGE(2), PGJ(2), and the PGI(2) analogue carbaprostacyclin (1-1000 nmol/L) exhibited no signific ant effects on cytokine production. However, the thromboxane A(2) (TXA(2)) agonists U46619 and carbocyclic (c)TXA(2) both stimulated WISH cytokine pro duction with similar potencies under basal or cytokine-stimulated condition s. Significant stimulation of IL-6 production was observed at concentration s greater than or equal to 8 nmol/L (P < .05 by analysis of variance), wher eas IL-8 production was stimulated significantly but to a lesser extent. Th e effects of U46619 and cTXA(2) were rapid; maximal stimulation of cytokine production occurred within 4 to 8 hours of treatment. U46619 augmented IL- 1 beta-stimulated IL-6 and IL-8 mRNA expression within 2 hours of treatment . In amnion explants inhibitors of TX synthesis and action abrogated the st imulatory effects of IL-1 beta on cytokine production. CONCLUSION: These results are consistent with the presence of a feed-forwar d loop in amnion involving TXA(2) and cytokines, which could play a signifi cant role in the progression of the inflammatory response involved int the mechanism of infection-driven preterm labor. Copyright (C) 2000 by the Soci ety for Gynecologic Investigation.