The human preovulatory follicle is a source of the chemotactic cytokine interleukin-8

Mammalian ovulation has several similarities to local inflammatory reactions, involving participation of leukocytes and inflammatory mediators. In response to a preovulatory luteinizing hormone surge, there is an influx of leukocytes into the preovulatory follicle and uncharacterized chemotactic activity towards these cells has previously been reported in follicular fluid of several species, including the human. In the present study, we have investigated the presence and local production of interleukin-8 (IL-8), a potent leukocyte-chemotactic and neutrophil-activating cytokine, in the human preovulatory follicle. Immunoreactive IL-8 was present in the follicular fluid in all of 12 in-vitro fertilization (IVF) patients investigated. IL-8 concentrations in follicular fluid (1269 +/- 245 pg/ml) were similar to 30-fold higher than in plasma (41 +/- 14 pg/ml). Isolated granulosa cells in culture secreted large amounts of IL-8 protein. Basal secretion of IL-8 was dose-dependently enhanced by the presence of fetal calf serum and was further stimulated by the addition of the ovulation-associated cytokine IL-1 beta. Messenger RNA for IL-8 was detected by reverse transcription/polymerase chain reaction (RT-PCR) in all tested samples of granulosa cells of IVF patients (n = 8) and in all biopsies from preovulatory follicle walls obtained in natural cycles (n = 6). This is the first demonstration of IL-8 in the mammalian ovary. Local production, combined with high follicular fluid concentrations, suggests that this cytokine plays a role in cyclic ovarian events, such as ovulation.