Effects of interleukin (IL)-6 on luteinizing hormone- and IL-1beta-induced ovulation and steroidogenesis in the rat ovary.

Evidence that cytokines have important roles in ovulation is accumulating, with various cytokines having been found to influence the ovulatory cascade. Interleukin (IL)-6 is a pluripotent cytokine involved in inflammatory reactions, and it has been demonstrated in high concentrations in human ovarian follicular fluid and in vitro in secretions from the ovary. We set out to determine the effect this cytokine has on ovulation rate and steroidogenesis in the in vitro-perfused rat ovary. Preovulatory ovaries were taken from eCG-primed animals, and ovulation was induced by LH (100 ng/ml) alone or in combination with cytokine. Ovaries in the IL-6/LH groups (IL-6 concentration of 0.19 nM or 1.9 nM) did not have ovulation rates different from ovaries in the LH-only group. Ovaries in the LH/IL-1beta group ovulated more oocytes than ovaries in the LH-only group (LH/IL-1beta =11+/-1.8 oocytes; LH alone=4.9+/-1.1; p=0.015) and the IL-6/LH/IL-1beta group (LH/IL-1beta/IL-6 [0.19 nM]=4+/-1.40; LH/IL-1beta=11+/-1.8; p=0.009). We have found that 1) exogenous IL-6 did not significantly alter the LH-induced ovulation rate but significantly reduced the LH/IL-1beta-induced ovulation rate; 2) exogenous IL-6 did not alter LH-induced progesterone levels measured at time points during the perfusion period, but the average increase in progesterone over basal level was stimulated by IL-6; 3) exogenous IL-6 did not affect LH-induced estradiol production; 4) exogenous IL-6 did not affect LH-induced androstenedione production but increased LH/IL-1beta-induced production; 5) exogenous IL-6 did not affect LH-induced prostaglandin E2 production. This study demonstrates that IL-6 does not play a role in regulating ovulation induced by LH in vitro but is capable of reducing LH/IL-1beta-enhanced ovulation rates. In addition, IL-6 may play a role in the regulation of ovarian steroid production.