Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process: Interleukin-8 induces neutrophil accumulation and activation in ovulation

The objective of our study was to elucidate the involvement of interleukin (IL)-8 in the hCG-induced rabbit ovulatory process. After administering hCG (100 IU i.v.), we examined myeloperoxidase (MPO) activity, which represents neutrophil accumulation; neutrophil elastase (NE) activity, which is an indicator of neutrophil activity; and levels of IL-8 in the ovaries. The maximal level of IL-8 was observed before MPO and NE activities reached a peak: production of IL-8, MPO, and NE activities peaked, respectively, at 4 h (5.58 ± 0.88 pg/mg ovary, n = 13), 6 h (1.07 ± 0.13 ΔA/min per gram ovary, n = 8), and 9 h (18.89 ± 1.05 U/g ovary, n = 8). Anti-rabbit IL-8 antiserum given i.v. significantly reduced the maximal levels of hCG-induced MPO activity (antiserum vs. control; 0.34 ± 0.04 vs. 1.12 ± 0.11 ΔA/min per gram ovary, n = 14, p < 0.001) and NE activity (8.14 ± 0.85 vs. 18.30 ± 0.79 U/g ovary, n = 14, p < 0.001). The hCG-induced ovulation rate was significantly inhibited by the antiserum (50.5% vs. 83.9%, n = 14, p < 0.001). Intraperitoneal injection of 100 mg/kg of ONO-5046, a specific NE inhibitor, also attenuated the ovulation rate (ONO-5046 vs. vehicle; 56.0% vs. 74.0%, n = 14, p < 0.05). These findings clearly indicate that IL-8 has an important role in the hCG-induced ovulatory process through the accumulation and activation of neutrophils.