Evidence that granulosa cells inhibit interleukin-1? and interleukin-2 production from follicular lymphomonocytes

Abstract

Relationships between immune and endocrine systems seem to occur in ovarian follicular fluids (FF). Lymphomonocytes have been found in preovulatory follicles and their specific products, cytokines [interleukin-1 (IL1), IL2], were demonstrated to inhibit steroidogenesis. Ovarian steroids, in turn, reduce the cytokine production from immune-competent cells. In the present study we evaluated whether lymphomonocytes are present in FF, and if both their subset distribution and their IL1 alpha and IL2 secretions, after activation with phytohemagglutinin (PHA), are similar to those of peripheral blood. Interferences of IL1 alpha and IL2 production by FF lymphomonocytes caused by isolated granulosa cells were also evaluated. The study was performed on 86 FFs obtained from follicles containing mature oocytes that were aspirated at the time of ovum pickup from 27 women undergoing controlled ovarian hyperstimulation with exogenous gonadotropins for an in vitro fertilization (IVF) program [IVF-embryo transfer (IVF-ET) or gamete intrafallopian transfer (GIFT)]. Lymphocytes were found in FF. The distribution of CD8+ and CD3+ lymphocyte subsets is equal to that in peripheral blood, but the percentage of CD11b+, CD16+, and CD4+ cells (its trend) is higher in FF than in peripheral blood. The amount of IL2 and IL1 alpha deriving from PHA-activated FF lymphomonocytes is similar to that of peripheral blood PHA-activated lymphomonocytes. Granulosa cells significantly blunt IL2 and IL1 alpha production by FF lymphomonocytes. These results suggest that preovulation, a migration of lymphomonocytes from the peripheral compartment to the follicle occurs. However, unfavorable effects of IL2 and IL1 alpha, cytotoxic and antisteroidogenetic activities, are counteracted by the products of granulosa cells. The higher amounts of CD11b+, CD16+, and CD4+ in FF suggest that they could be involved in other immune processes.