INTERLEUKIN (IL)-6 AND IL-8 PRODUCTION BY HUMAN AMNION - REGULATION BY CYTOKINES, GROWTH-FACTORS, GLUCOCORTICOIDS, PHORBOL ESTERS, AND BACTERIAL LIPOPOLYSACCHARIDE

Amniotic fluid at term contains high concentrations of interleukin (IL )-6 and IL-8. The source of these cytokines has not been identified, a lthough the fetal membranes (amnion and chorion) are likely contributo rs. Amnion cytokine production was investigated by using amnion cells isolated by enzymatic digestion (from placentas delivered at term befo re labor) and cultured in vitro. IL-6 and IL-8 were measured in condit ioned media by ELISA. Amnion cells produced detectable amounts of both IL-6 and IL-8 throughout the 7-day culture period. The ratio of IL-8 to IL-6 was approximately 5:1, similar to the ratio found in amniotic fluid. Production of both IL-6 and IL-8 was stimulated in a concentrat ion-dependent fashion by interleukin-1 beta (0.1-10 ng/ml), tumor necr osis factor-alpha (1-100 ng/ml), and bacterial lipopolysaccharide (0.1 -10 mu g/ml), and also by 100 nM phorbol 12-myristate 13-acetate. Epid ermal growth factor (1-25 ng/ml) had only minimal effects on amnion cy tokine production. Dexamethasone (10 nM) inhibited IL-6/-8 production by approximately 50% throughout the culture period. Production of IL-6 /-8 by cultured amniotic fibroblasts, which under basal conditions was much lower than that by epithelial cells, was regulated by all the ag ents tested in a fashion similar to that of the epithelial cells. Thes e findings suggest that the amnion contributes to the pool of IL-6 and IL-8 in amniotic fluid. We speculate that amnion-derived cytokines mi ght have functions during normal human parturition that are distinct f rom their conventional roles as inflammatory mediators.