Endometrial expression and secretion of interleukin-6 throughout the menstrual cycle

Previous findings revealing reduced endometrial interleukin-6 (IL-6) mRNA expression in patients with recurrent early abortions gave rise to the analysis of IL-6 synthesis in the human endometrium, and how it relates to concentrations in uterine secretions. Endometrial tissues and uterine secretions were collected from patients undergoing hysterectomy. Expression of IL-6 receptor and gp130 mRNA (n = 28) in total endometrium, of IL-6 mRNA in endometrial epithelial and stromal cells, and CD45-positive leukocytes were investigated by RNAase protection assay throughout the cycle. IL-6 protein was assessed in endometrial tissue by immunohistochemistry (n = 32) and in uterine secretions by enzyme-linked immunosorbent assay (ELISA) (n = 33). IL-6 mRNA was expressed at low levels in the proliferative phase, and expression increased progressively in the secretory phase. The increase was attributed to epithelial and stromal cells and leukocytes. Concentrations of IL-6 protein in endometrial glands and in uterine secretions were low in the proliferative phase, and increased 5-10-fold in the mid- to late secretory phase. mRNA expression of IL-6 receptor and gp130 remained constant in total endometrium throughout the menstrual cycle. High concentrations of IL-6 in the mid-secretory phase, the putative implantation window, and a further increase in the late secretory phase, the premenstrual period, support a role of IL-6 in the regulation of endometrial functions.