Synergistic effect of interleukin (IL)-1α and ceramide analogue on the production of IL-6, IL-8, and macrophage colony-stimulating factor by endometrial stromal cells

Objective: To measure the level of interleukin 6 (IL-6), IL-8, and macrophage colony-stimulating factor (M-CSF) induced by IL-1alpha in endometrial stromal cells (ESC) following treatment with ceramide analogues. Design: The effects of IL-1alpha, IL-1 receptor antagonist (IL-1RA), C2-ceramide, and C6-ceramide on the production of IL-6, IL-8, and M-CSF by ESC. Setting: Research laboratory at Oita University Medical School. Patient(s): Eleven premenopausal women who had undergone hysterectomies for subserous myoma provided endometrial specimens in the secretory phase. Intervention(s): The ESC were incubated for 24 hours with IL-1alpha, IL-1RA, C2-ceramide, and C6-ceramide. Main Outcome Measure(s): The levels of IL-6, IL-8, and M-CSF in the culture media were measured via enzyme-linked immunoabsorbent assay. Result(s): Following stimulation by IL-1alpha, the production of IL-6, IL-8, and M-CSF showed a statistically significant increase, and they were suppressed by IL-1RA in a dose-dependent manner. Production of IL-6, IL-8, and M-CSF was not statistically significantly increased by IL-1alpha plus C2-ceramide as compared with IL-1alpha alone. Production of both IL-8 and M-CSF was statistically significantly increased by IL-1alpha plus C6-ceramide as compared with IL-1alpha alone; however, IL-6 production was not increased. Conclusion(s): The results suggest that IL-1alpha stimulates the production of IL-8 and M-CSF by a mechanism that involves the sphingomyelin-ceramide system. Ceramide may be important in increasing the production of IL-8 and M-CSF in the human endometrium. (C) 2004 by American Society for Reproductive Medicine.