STIMULATION OF HUMAN ENDOMETRIAL EPITHELIAL-CELL INTERLEUKIN-6 PRODUCTION BY INTERLEUKIN-1 AND PLACENTAL PROTEIN-14

The effect of interleukin 1 (IL1) and placental protein 14 (PP14) on the production of interleukin 6 (IL6) by cultured human endometrial epithelial cells prepared from endometrial biopsy material obtained at different stages in the menstrual cycle was investigated. Basal IL6 production by cells prepared from proliferative endometrium was greater than that produced by cells prepared from secretory endometrium (7.3 +/- 0.3 and 1.1 +/- 0.2 ng/well/24 h respectively, P < 0.001). IL1 (0.025-2.5 ng/ml) caused a dose-dependent increase in IL6 production by cells prepared from both proliferative and secretory endometrium, but cells prepared from secretory endometrium responded to a lower concentration of IL1 than those prepared from proliferative endometrium. IL1-stimulated IL6 production by epithelial cells prepared from secretory endometrium typically reached 10 times basal values, while in cells prepared from proliferative endometrium stimulated levels were approximately twice the basal values. PP14 (1-50 mu g/ml) also caused a dose-dependent increase in IL6 production by epithelial cells prepared from secretory endometrium, but had no effect on IL6 production by cells prepared from proliferative endometrium. Even in secretory cells PP14 was less effective than IL1 at stimulating IL6 production, with stimulated levels only reaching twice the basal values. This suggests that PP14 and IL1 act via different mechanisms in the stimulation of IL6 production. The results show that IL6 production by human endometrial epithelial cells is stimulated by other immunomodulatory peptides and this may be part of the network of such peptides in the endometrium which may influence embryo implantation.