Preovulatory human follicular fluid in vitro inhibits interleukin (IL)- 1α, IL-2, and production and expression of p55 chain IL-2 receptor of lymphomonocytes

Objective: To evaluate the immunoactivity of human follicular fluids (FFs) of ovaries stimulated with exogenous gonadotropins. Participants: Follicular fluids and peripheral blood mononuclear cells (PBMCs) were obtained at the time of ovum pick-up from 15 women (25 to 34 years of age) undergoing gonadotropin stimulation for GIFT. Methods: The evaluation of the blastic response of PBMC to phytohemagglutinin (PHA), PHA plus recombinant interleukin (IL)-2, and recombinant IL-2 alone was performed by measuring 3H thymidine (3H-TdR) incorporation by the cells cultured in media with or without FF. The percentage of CD25 expression on PHA-stimulated T lymphocytes was evaluated by flow cytofluorometry. The levels of IL-1α and IL-2 in supernatants from PHA-stimulated PBMC were evaluated by an ELISA. Results: The PBMC blastic response to PHA, to recombinant IL-2 alone, and to PHA plus recombinant IL-2 was suppressed by the addition of FF. However, the percentage of inhibition of 3H-TdR incorporation induced by FF in cultures performed in the presence of PHA alone was significantly higher than that obtained in cultures performed in the presence of PHA plus recombinant IL-2. The percentage of expression of the CD25 on PHA-stimulated lymphocytes was also significantly lower in presence of FF in comparison with the controls. Similarly, the production of IL-1α and IL-2 in culture media of PHA- stimulated PBMC was significantly lower when FF was added in culture medium. Conclusions: The present data confirm that preovulatory FFs obtained by gonadotropin-stimulated ovaries contain unknown factors that induce immunosuppression. Furthermore, our study explains that the immunosuppressive activity of FF is mediated by the specific inhibition of the production of IL-1α and IL-2 and by the decreased expression of the CD25