Effects of indomethacin on ovarian leukocytes during the periovulatory period in the rat

We have investigated the effects of indomethacin (IM), a non-steroidal anti-inflammatory drug, and the role of prostaglandins on the accumulation of leukocytes in the rat ovary during the periovulatory period. Adult cycling rats were injected sc with 1 mg of IM in olive oil or vehicle on the morning of proestrus. Some animals were killed at 16:00 h in proestrus. On the evening (19:00 h) of proestrus, IM-treated rats were injected with 500 micrograms of prostaglandin E1 in saline or vehicle. Animals were killed at 01:30 and 09:00 h in estrus. There was an influx of macrophages, neutrophils, and eosinophils into the theca layers of preovulatory follicles, and of neutrophils and eosinophils into the ovarian medulla from 16:00 h in proestrus to 01:30 h in estrus. All these changes, except the accumulation of neutrophils in the theca layers of preovulatory follicles, were blocked by IM treatment. At 09:00 h in estrus, large clusters of neutrophils were observed in IM-treated rats, around abnormally ruptured follicles. The accumulation of leukocytes was not restored by prostaglandin supplementation, despite the inhibition of abnormal follicle rupture and restoration of ovulation in these animals. These results suggest that different mechanisms are involved in leukocyte accumulation in the ovary during the periovulatory period, and that the inhibitory effects of IM on the influx of leukocytes are not dependent on prostaglandin synthesis inhibition.